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Ou H, Zhuang J, Jian M, Zheng X, Wu T, Cheng H, Qian R. Perioperative versus adjuvant chemotherapy for resectable gastric cancer: a meta-analysis of randomized controlled trials. Front Oncol 2025; 15:1432596. [PMID: 40115020 PMCID: PMC11922704 DOI: 10.3389/fonc.2025.1432596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
Objectives To report the latest systematic review and meta-analysis of randomized controlled trials (RCT) to compare perioperative versus adjuvant chemotherapy for resectable gastric cancer. Methods We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2024 for RCT which compared perioperative versus adjuvant chemotherapy for resectable gastric cancer. Outcomes measured were overall survival (OS) and progression-free survival (PFS). Results 5 RCTs including 2,735 patients were included for meta-analysis. Meta-analysis revealed a significant longer PFS in the neoadjuvant chemotherapy (NAC) group (HR: 0.77; 95% CI: 0.69, 0.85; P<0.00001) compared with adjuvant chemotherapy (AC) group. Subgroup analysis found that there was still a significant superiority of NAC in female (HR: 0.53; 95% CI: 0.40, 0.70; P<0.0001) and cN+ (HR: 0.77; 95% CI: 0.67, 0.89; P=0.0005) patients, while the superiority disappeared in male (HR: 0.87; 95% CI: 0.74, 1.01; P=0.07) and cN- patients (HR: 0.91; 95% CI: 0.46, 1.78; P=0.77). In addition, meta-analysis observed a trend towards improved OS with NAC (HR: 0.86; 95% CI: 0.70, 1.07; P = 0.17), and sensitivity analysis demonstrated instability in OS. Conclusions NAC can significantly prolong PFS in patients with resectable gastric cancer compared to AC, and the benefit is more significant in women and cN+ patients. Besides, our analysis indicated that NAC has a potential to improve OS compared with AC. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024546165.
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Affiliation(s)
- Haiya Ou
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Jiamei Zhuang
- Department of Nephrology, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Mingwei Jian
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xinyi Zheng
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Tingping Wu
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Honghui Cheng
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Rui Qian
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
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Wei C, Du X, Hu J, Dong Y, Chen Y, Cao B. Perioperative chemotherapy versus adjuvant chemotherapy in patients with resectable gastric cancer: A systematic review with meta-analysis. Crit Rev Oncol Hematol 2024; 198:104082. [PMID: 37532103 DOI: 10.1016/j.critrevonc.2023.104082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/01/2023] [Accepted: 07/30/2023] [Indexed: 08/04/2023] Open
Abstract
PURPOSE The study aimed to investigate the prognosis and safety of perioperative chemotherapy (PC) compared with adjuvant chemotherapy (AC). METHODS We systematically searched and assessed studies in PubMed, Embase, and the Cochrane Library from inception to 1st September 2022. RESULTS Eighteen studies were eligible for the analysis, including 4686 patients in total. Our study found that patients with resectable gastric cancer undergoing PC had favorable prognosis on OS (HR 0.77; 95% CI 0.69-0.87) and DFS (HR 0.76; 95% CI 0.69-0.84) than those who undergoing AC. Addition of neoadjuvant chemotherapy (NAC) to AC provided higher R0 resection rate but did not increase the risk of postoperative complication rate and most of the adverse event rates. CONCLUSION Our study demonstrated that PC shows better OS and DFS in Asians with resectable gastric cancer compared with AC. PC should be preferred because of its favorable prognosis and similar safety.
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Affiliation(s)
- Chenyu Wei
- Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Xuelin Du
- Clinical Trial Institution, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Jiexuan Hu
- Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Yin Dong
- Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Yan Chen
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Bangwei Cao
- Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
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Yu Z, Tu H, Qiu S, Dong X, Zhang Y, Ma C, Li P. Multidisciplinary treatment for locally advanced gastric cancer: A systematic review and network meta-analysis. J Minim Access Surg 2023; 19:335-347. [PMID: 37282430 PMCID: PMC10449051 DOI: 10.4103/jmas.jmas_170_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 01/10/2023] [Accepted: 03/27/2023] [Indexed: 06/08/2023] Open
Abstract
Introduction This study aimed to evaluate the efficacy of multidisciplinary treatment for patients with locally advanced gastric cancer (LAGC) who underwent radical gastrectomy. Patients and Methods Randomised controlled trials (RCTs) comparing the effectiveness of surgery alone, adjuvant chemotherapy (CT), adjuvant radiotherapy (RT), adjuvant chemoradiotherapy (CRT), neoadjuvant CT, neoadjuvant RT, neoadjuvant CRT, perioperative CT and hyperthermic intraperitoneal chemotherapy (HIPEC) for LAGC were searched. Overall survival (OS), disease-free survival (DFS), recurrence and metastasis, long-term mortality, adverse events (grade ≥3), operative complications and R0 resection rate were used as outcome indicators for meta-analysis. Results Forty-five RCTs with 10077 participants were finally analysed. Adjuvant CT had higher OS (hazard ratio [HR] = 0.74, 95% credible interval [CI] = 0.66-0.82) and DFS (HR = 0.67, 95% CI = 0.60-0.74) than surgery-alone group. Perioperative CT (odds ratio [OR] = 2.56, 95% CI = 1.19-5.50) and adjuvant CT (OR = 0.48, 95% CI = 0.27-0.86) both had more recurrence and metastasis than HIPEC + adjuvant CT, while adjuvant CRT tended to have less recurrence and metastasis than adjuvant CT (OR = 1.76, 95% CI = 1.29-2.42) and even adjuvant RT (OR = 1.83, 95% CI = 0.98-3.40). Moreover, the incidence of mortality in HIPEC + adjuvant CT was lower than that in adjuvant RT (OR = 0.28, 95% CI = 0.11-0.72), adjuvant CT (OR = 0.45, 95% CI = 0.23-0.86) and perioperative CT (OR = 2.39, 95% CI = 1.05-5.41). Analysis of adverse events (grade ≥3) showed no statistically significant difference between any two adjuvant therapy groups. Conclusion A combination of HIPEC with adjuvant CT seems to be the most effective adjuvant therapy, which contributes to reducing tumour recurrence, metastasis and mortality - without increasing surgical complications and adverse events related to toxicity. Compared with CT or RT alone, CRT can reduce recurrence, metastasis and mortality but increase adverse events. Moreover, neoadjuvant therapy can effectively improve the radical resection rate, but neoadjuvant CT tends to increase surgical complications.
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Affiliation(s)
- Zhiyuan Yu
- School of Medicine, Nankai University, Nankai District, Tianjin, China
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Huaiyu Tu
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Shuzhong Qiu
- Medical School of Chinese PLA, Haidian District, Beijing, China
| | - Xiaoyu Dong
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Yonghui Zhang
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Chao Ma
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Peiyu Li
- School of Medicine, Nankai University, Nankai District, Tianjin, China
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
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Singh HK, Chaudhari V, Batra S, Ostwal V, Ramaswamy A, Mokal S, Shrikhande SV, Bhandare MS. Radical D2 gastrectomy with adjuvant chemotherapy for stage IB/II/III distal gastric cancers in the era of perioperative chemotherapy: A propensity matched comparison. Am J Surg 2022; 223:1055-1062. [PMID: 34756584 DOI: 10.1016/j.amjsurg.2021.10.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 10/06/2021] [Accepted: 10/22/2021] [Indexed: 01/26/2023]
Abstract
AIM This study aimed to assess the impact of treatment sequencing on long-term survival, in distal gastric cancers (GCs) (stage IB/II/III). METHODS This retrospective study included patients with distal GC undergoing D2 resection. Outcomes were compared between group 1 (surgery with adjuvant chemotherapy) and group 2 (perioperative chemotherapy with surgery). 1:1 matching for baseline characteristics (age, cT, and cN stage) was performed for outcome comparison. RESULTS At a median follow-up of 47.5 months in the included 342 patients, the 5-year overall survival (OS) was 61.1% and disease-free survival (DFS) was 50.5%. OS was comparable in the unmatched (group 1, n = 118; group 2, n = 224) (HR 0.905, 95%CI 0.64-1.33, P = 0.615) and matched groups (group 1, n = 97; group 2, n = 97) (HR 0.77, 95% CI 0.48-1.26, P = 0.3). CONCLUSION D2 resection followed by adjuvant chemotherapy provides similar long-term outcomes as compared to perioperative chemotherapy approach for stage IB/II/III distal GCs.
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Affiliation(s)
- Hemant Kumar Singh
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India; Department of Surgical Oncology, All India Institute of Medical Sciences, Mangalagiri, Guntur, 522503, India
| | - Vikram Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Swati Batra
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Smruti Mokal
- Clinical Research Secretariat, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India.
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Bauer K, Manzini G, Henne-Bruns D, Buechler P. Perioperative chemotherapy for advanced gastric cancer - results from a tertiary-care hospital in Germany. World J Gastrointest Oncol 2020; 12:559-568. [PMID: 32461787 PMCID: PMC7235186 DOI: 10.4251/wjgo.v12.i5.559] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 03/18/2020] [Accepted: 04/09/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neoadjuvant/perioperative chemotherapy is the recommended treatment for advanced stages of gastric cancer (> T2, N+) before tumour resection in many European guidelines. However, there is no consensus as to whether perioperative chemotherapy is as effective in distal as in proximal tumours, in addition to a relevant uncertainty concerning appropriate treatment modalities for elderly patients.
AIM To investigate the role of perioperative chemotherapy in advanced gastric cancer in patients from a German tertiary clinic with respect to efficacy, localisation, and age.
METHODS We performed a retrospective analysis of 158 patients from our clinic with adenocarcinoma of the stomach or the gastroesophageal junction who underwent resection between 2008 and 2016. The data were evaluated particularly in relation to patient age, tumour site, and perioperative therapy.
RESULTS Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population. The 5-year survival rates were 40% for patients who received perioperative chemotherapy and 29% for the group without perioperative chemotherapy (P = 0.125). Our patients were on average distinctly older than patients in most of the published randomised controlled trials. Patients elder than 75 years received perioperative chemotherapy far less frequently. Patients with a proximal tumour received perioperative chemotherapy much more often.
CONCLUSION This analysis reconfirms our previous data concerning the effectiveness of perioperative chemotherapy for advanced gastric cancer. There is reasonable doubt that the quality of the existing randomized controlled trials is sufficient to generally justify perioperative chemotherapy in patients with advanced gastric cancer independent of tumour localization or age.
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Affiliation(s)
- Katrin Bauer
- Department for General, Visceral, Thoracic and Paediatric Surgery, Clinic of Kempten, Kempten 87439, Germany
| | - Giulia Manzini
- Department of General and Visceral Surgery, University Hospital of Ulm, Ulm 89081, Germany
| | - Doris Henne-Bruns
- Department of General and Visceral Surgery, University Hospital of Ulm, Ulm 89081, Germany
| | - Peter Buechler
- Department for General, Visceral, Thoracic and Paediatric Surgery, Clinic of Kempten, Kempten 87439, Germany
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Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials. Int J Surg 2018; 51:120-127. [PMID: 29413875 DOI: 10.1016/j.ijsu.2018.01.008] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 01/07/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Even in after curative surgery and adequate linfoadenectomy the survival of advanced gastric cancer (AGC) remains poor. At present some data have been published on the effects of NACT and perioperative chemotherapy on AGC and Esophago-gastric cancer (EGC) but not definitive ones. The present meta-analysis aims to evaluate the effects of neoadjuvant chemotherapy (NACT) on the AGC and EGC. MATERIAL AND METHODS A systematic review with meta-analysis of randomized controlled trials (RCTs) of NACT + surgery vs. Surgery in patients with AGC and EGC was performed. RESULTS 15 RCTs have been included (2001 patients: 977 into NACT + surgery arm and 1024 into control arm). NACT + Surgery reduces the overall mortality at 1, 3 and 5-year in cumulative analysis (RR = 0.78; 0.81; 0.88 respectively), at 1, 2, 3 and 5-years in EGC (RR = 0.79; 0.83; 0.84; 0.91 respectively) and at 3 and 5-years in AGC (RR = 0.74; 0.82 respectively). Morbidity and perioperative mortality rate are not influenced by NACT. Recurrence rate is reduced by NACT + surgery in EGC (RR = 0.80). CONCLUSIONS NACT reduces the mortality in gastric and esophago-gastric cancer. Morbidity and perioperative mortality are not influenced by NACT. The overall recurrence rate is reduced by NACT in esophago-gastric cancer.
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Miao ZF, Liu XY, Wang ZN, Zhao TT, Xu YY, Song YX, Huang JY, Xu H, Xu HM. Effect of neoadjuvant chemotherapy in patients with gastric cancer: a PRISMA-compliant systematic review and meta-analysis. BMC Cancer 2018; 18:118. [PMID: 29385994 PMCID: PMC5793339 DOI: 10.1186/s12885-018-4027-0] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 01/23/2018] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is extensively used in the treatment of patients with gastric cancer (GC), particularly in high risk, advanced gastric cancer. Previous trials testing the efficacy of NAC have reported inconsistent results. METHODS This study compares the combined use of NAC and surgery with surgery alone for GC by using a meta-analytic approach. We performed an electronic search of PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials (RCTs) on NAC published before Oct 2015. The primary outcome of the studies was data on survival rates for patients with GC. The summary results were pooled using the random-effects model. We included 12 prospective RCTs reporting data on 1538 GC patients. RESULTS Patients who received NAC were associated with significant improvement of OS (P = 0.001) and PFS (P < 0.001). Furthermore, NAC therapy significantly increased the incidence of 1-year survival rate (SR) (P = 0.020), 3-year SR (P = 0.011), and 4-year SR (P = 0.001). Similarly, NAC therapy was associated with a lower incidence of 1-year (P < 0.001), 2-year (P < 0.001), 3-year (P < 0.001), 4-year (P = 0.001), and 5-year recurrence rate (P = 0.002). Conversely, patients who received NAC also experienced a significantly increased risk of lymphocytopenia (P = 0.003), and hemoglobinopathy (P = 0.021). CONCLUSIONS The findings of this study suggested that NAC is associated with significant improvement in the outcomes of survival and disease progression for GC patients while also increasing some toxicity.
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Affiliation(s)
- Zhi-Feng Miao
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Xing-Yu Liu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Zhen-Ning Wang
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Ting-Ting Zhao
- Department of Breast Surgery, First Hospital of China Medical University, Shenyang, China
| | - Ying-Ying Xu
- Department of Breast Surgery, First Hospital of China Medical University, Shenyang, China
| | - Yong-Xi Song
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Jin-Yu Huang
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Hao Xu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Hui-Mian Xu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
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Reddavid R, Sofia S, Chiaro P, Colli F, Trapani R, Esposito L, Solej M, Degiuli M. Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake? World J Gastroenterol 2018; 24:274-289. [PMID: 29375213 PMCID: PMC5768946 DOI: 10.3748/wjg.v24.i2.274] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 12/13/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.
METHODS We proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival (DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment.
RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the period from January 1993 - March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node (LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. In the third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the “Study Treatment” protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction (EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients’ populations are even higher than the survival rates reported after NAC followed by incomplete surgery.
CONCLUSION NAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicine-related demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended (D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.
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Affiliation(s)
- Rossella Reddavid
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Silvia Sofia
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Paolo Chiaro
- Department of Surgical Sciences, Digestive and Oncological Surgery, University of Turin, Molinette Hospital, Turin 10126, Italy
| | - Fabio Colli
- Department of Surgical Sciences, Digestive and Oncological Surgery, University of Turin, Molinette Hospital, Turin 10126, Italy
| | - Renza Trapani
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Laura Esposito
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Mario Solej
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Maurizio Degiuli
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
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Zhao JH, Gao P, Song YX, Sun JX, Chen XW, Ma B, Yang YC, Wang ZN. Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis. BMC Cancer 2016; 16:631. [PMID: 27519527 PMCID: PMC4983077 DOI: 10.1186/s12885-016-2667-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 08/02/2016] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. METHODS We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy. RESULTS Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95 % CI, 0.61 to 0.89; P < 0.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95 % CI, 0.46 to 0.76; P < 0.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95 % CI, 0.56 to 1.55; P = 0.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95 % CI, 0.63 to 1.51; P = 0.91) or adverse effects of chemotherapy (P > 0.05 for all adverse effects). CONCLUSION Perioperative chemotherapy showed improved survival compared to adjuvant chemotherapy for gastric cancer. In addition, combination chemotherapy resulted in better survival compared to monotherapy in the neoadjuvant chemotherapy regimens.
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Affiliation(s)
- Jun-hua Zhao
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
| | - Peng Gao
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
| | - Yong-xi Song
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
| | - Jing-xu Sun
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
| | - Xiao-wan Chen
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
| | - Bin Ma
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
| | - Yu-chong Yang
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
| | - Zhen-ning Wang
- Department of Surgical Oncology and General Surgery, the First Hospital of China Medical University, Shenyang, 110001 People’s Republic of China
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Yang Y, Yin X, Sheng L, Xu S, Dong L, Liu L. Perioperative chemotherapy more of a benefit for overall survival than adjuvant chemotherapy for operable gastric cancer: an updated Meta-analysis. Sci Rep 2015; 5:12850. [PMID: 26242393 PMCID: PMC4525358 DOI: 10.1038/srep12850] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Accepted: 04/27/2015] [Indexed: 12/18/2022] Open
Abstract
To clarify the effect of neoadjuvant chemotherapy (NAC) on the survival outcomes of operable gastric cancers, we searched PubMed, Embase, and Cochrane Library for randomized clinical trials published until June 2014 that compared NAC-containing strategies with NAC-free strategies in patients with adenocarcinoma of the stomach or the esophagogastric junction, who had undergone potentially curative resection. The adjusted pooled hazard ratio (HR) for overall survival (OS) was insignificant when comparing the NAC-containing arm with the NAC-free arm. Subgroup analysis showed that the OS of the treatment arm that involved both adjuvant chemotherapy (AC) and NAC was significantly improved over the control arm (AC only) (HR = 0.48, 95% CI: 0.35-0.67; P < 0.001). While NAC alone plus surgery did not show any survival benefit over surgery alone. Perioperative chemotherapy (PC) also showed a significant increase in PFS and a significant reduction in distant metastasis compared to surgery alone. Therefore, in patients with resectable gastric cancer, NAC alone is not enough and AC alone is not good enough to definitely improve their OS. Collectively, PC combined with surgery could maximize the survival benefit for patients with resectable gastric cancer.
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Affiliation(s)
- Ya’nan Yang
- Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China
| | - Xue Yin
- Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China
| | - Lei Sheng
- Cancer Therapeutics Laboratory, Centre for Personalized Cancer Medicine, School of Medicine, University of Adelaide, Australia
| | - Shan Xu
- Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China
| | - Lingling Dong
- Department of Cancer, Weifang Traditional Chinese Medical Hospital, Weifang, China
| | - Lian Liu
- Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China
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Xiong B, Ma L, Huang W, Cheng Y, Zhao Q, Liu J. WITHDRAWN: Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: An updated meta-analysis of 12 randomized controlled trials. Surg Oncol 2014:S0960-7404(14)00097-8. [PMID: 25515042 DOI: 10.1016/j.suronc.2014.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 10/16/2014] [Accepted: 11/23/2014] [Indexed: 11/20/2022]
Abstract
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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Affiliation(s)
- Binghong Xiong
- Department of General Surgery, Peking University Shougang Hospital, No 9 Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, PR China.
| | - Li Ma
- Department of Endocrinology, The Third Hospital of Mianyang, Sichuan Province, Mianyang, 621000, PR China
| | - Wei Huang
- Department of General Surgery, The Ninth People's Hospital of Chongqing City, Chongqing 400070, PR China
| | - Yong Cheng
- Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University, No 1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, PR China.
| | - Qikang Zhao
- Department of General Surgery, Peking University Shougang Hospital, No 9 Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, PR China
| | - Jingshan Liu
- Department of General Surgery, Peking University Shougang Hospital, No 9 Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, PR China
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Nakajima T, Fujii M. What make differences in the outcome of adjuvant treatments for resected gastric cancer? World J Gastroenterol 2014; 20:11567-11573. [PMID: 25206264 PMCID: PMC4155350 DOI: 10.3748/wjg.v20.i33.11567] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 01/09/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery.
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Xiong BH, Cheng Y, Ma L, Zhang CQ. An Updated Meta-Analysis of Randomized Controlled Trial Assessing the Effect of Neoadjuvant Chemotherapy in Advanced Gastric Cancer. Cancer Invest 2014; 32:272-84. [DOI: 10.3109/07357907.2014.911877] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by surgery for advanced gastric cancer patients with para-aortic lymph node metastasis. Cancer Chemother Pharmacol 2014; 73:1155-61. [PMID: 24748418 PMCID: PMC4032640 DOI: 10.1007/s00280-014-2449-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Accepted: 03/11/2014] [Indexed: 12/19/2022]
Abstract
Purpose Gastric cancer with para-aortic lymph node (PAN) involvement is regarded as advanced disease, and only chemotherapy is recommended from the guidelines. In unresectable cases, neoadjuvant chemotherapy could prolong survival if conversion to resectability could be achieved. Methods The study was a single-arm phase II trial. Patients who were diagnosed with gastric cancer and PAN involvement (Stations No. 16a2/16b1) were treated with capecitabine and oxaliplatin combination chemotherapy every 3 weeks for a maximum of six cycles. After every two cycles, abdominal computed tomographic scans were repeated to evaluate the response, and surgery was performed at the physician’s discretion in patients with sufficient tumor response, followed by chemotherapy with the same regimen to complete a total of six cycles. The primary end point was the response rate of the preoperative chemotherapy. The secondary end points were R0 resection rate, progression-free survival (PFS), overall survival (OS), and adverse events. Results A total of 48 patients were enrolled. The response rate of the first-line chemotherapy was 49.0 %, and the clinical benefit response was 85.1 %. After a median of four cycles of chemotherapy, 28 patients received surgery (58.3 %). The median PFS and OS of all patients were 10.0 and 29.8 months, respectively. Patients in the surgery group had much longer PFS (18.1 vs. 5.6 mo, P = 0.001) and OS (not reached vs. 12.5 mo, P = 0.016) compared with those in the non-surgery group. Conclusions For gastric cancer patients with PAN involvement, neoadjuvant chemotherapy with XELOX demonstrated a good response rate, and a sufficient R0 resection rate, with acceptable toxicities. Further study is needed to confirm the effectiveness of this regimen.
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Xiong B, Ma L, Cheng Y, Zhang C. Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: an updated meta-analysis of randomized controlled trials. Eur J Surg Oncol 2014; 40:1321-30. [PMID: 25239442 DOI: 10.1016/j.ejso.2014.01.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2013] [Revised: 12/19/2013] [Accepted: 01/05/2014] [Indexed: 12/19/2022] Open
Abstract
AIMS To assess the efficacy and safety of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC). METHODS By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC-combined surgery versus surgery alone in AGC were included. All calculations and statistical tests were performed using RevMan 5.0 software. RESULTS 12 RCTs with a total of 1820 patients were included. All patients had locally advanced but resectable gastric cancer and received NAC. NAC can slightly improve the survival rate (OR = 1.32, 95% confidence interval (CI): 1.07-1.64, P = 0.01), with little or no significant benefits in subgroup analyses between either different population or regimens. NAC can significantly improve the 3-year progression-free survival (PFS) (OR: 1.85, 95% CI: 1.39-2.46, p < 0.0001), tumor down-staging rate (OR: 1.71, 95% CI: 1.26, 2.33, p = 0.0006) and R0 resection rate (OR: 1.38, 95% CI: 1.08-1.78, P = 0.01) of patients with AGC. There was no difference between the two arms, in terms of relapse rates (OR: 1.03, 95% CI: 0.60-1.78, p = 0.92), operative complications (OR: 1.20, 95% CI: 0.90-1.58, p = 0.21), perioperative mortality (OR: 1.14, 95% CI: 0.64-2.05, p = 0.65) and grade 3/4 adverse effects: gastrointestinal problem (OR: 0.57, 95% CI: 0.25-1.30, p = 0.18), leukopenia (OR: 0.88, 95% CI: 0.41-1.91, p = 0.75), thrombocytopenia (OR: 1.27, 95% CI: 0.27-5.93, p = 0.76). CONCLUSION NAC is effective and safe. However, further prospective multi-national and multi-center RCTs are still needed in order to investigate the long-term oncological and functional outcomes to define the clinical benefits of NAC and the most effective strategies for AGC.
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Affiliation(s)
- B Xiong
- Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, PR China.
| | - L Ma
- Department of Internal Medicine, Chongqing Huaxi Hospital, Banan District, Chongqing 400054, PR China
| | - Y Cheng
- Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, PR China.
| | - C Zhang
- Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, PR China.
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Xu AM, Huang L, Liu W, Gao S, Han WX, Wei ZJ. Neoadjuvant chemotherapy followed by surgery versus surgery alone for gastric carcinoma: systematic review and meta-analysis of randomized controlled trials. PLoS One 2014; 9:e86941. [PMID: 24497999 PMCID: PMC3907439 DOI: 10.1371/journal.pone.0086941] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 12/16/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC. METHODS We systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed. RESULTS A total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65-1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20-3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment. CONCLUSIONS NAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn't support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.
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Affiliation(s)
- A-Man Xu
- Anhui Medical University, Hefei, China
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Lei Huang
- Anhui Medical University, Hefei, China
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wei Liu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuang Gao
- Anhui Medical University, Hefei, China
- Department of Medical Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wen-Xiu Han
- Anhui Medical University, Hefei, China
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhi-Jian Wei
- Anhui Medical University, Hefei, China
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Xu AM, Huang L, Liu W, Gao S, Han WX, Wei ZJ. Neoadjuvant chemotherapy followed by surgery versus surgery alone for gastric carcinoma: systematic review and meta-analysis of randomized controlled trials. PLoS One 2014. [PMID: 24497999 DOI: 10.1371/journal.pone.0086941.ecollection] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC. METHODS We systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed. RESULTS A total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65-1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20-3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment. CONCLUSIONS NAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn't support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.
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Affiliation(s)
- A-Man Xu
- Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Lei Huang
- Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wei Liu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuang Gao
- Anhui Medical University, Hefei, China ; Department of Medical Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wen-Xiu Han
- Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhi-Jian Wei
- Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Zhang CD, Zeng YJ, Li HW, Zhao ZM, Zhang JK, Dai DQ. Neoadjuvant Chemotherapy for Nonmetastatic Esophago-Gastric Adenocarcinomas: A Systematic Review and Meta-Analysis. Cancer Invest 2013; 31:421-31. [DOI: 10.3109/07357907.2013.802801] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Liao Y, Yang ZL, Peng JS, Xiang J, Wang JP. Neoadjuvant chemotherapy for gastric cancer: a meta-analysis of randomized, controlled trials. J Gastroenterol Hepatol 2013; 28:777-82. [PMID: 23425049 DOI: 10.1111/jgh.12152] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/11/2013] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer. METHODS We searched systematically electronic through the databases of PUBMED, EMBASE, China Biological Medicine, and China National Knowledge Infrastructure Whole Article for studies published from 1975. Two reviewers independently evaluated the relevant reports and searched manually reference from these reports for additional trials. Outcomes assessed by meta-analysis included overall survival rate, progression-free survival rate, R0 resection rate, downstaging effect, postoperative complications, and perioperative mortality. RESULTS Six randomized, controlled trials with 781 patients were included in the meta-analysis. Odds ratio (95% confidence interval; P-value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone, was 1.16 (0.85-1.58; P = 0.36) for overall survival, 1.24 (0.78-1.96; P = 0.36) for R0 resection, 1.25 (0.75-2.09; P = 0.39) for postoperative complications, and 3.60 (0.59-22.45; P = 0.17) for perioperative mortality. CONCLUSIONS Compared with surgery alone, neoadjuvant chemotherapy followed by surgery was not associated with a higher rate of overall survival or complete resection (R0 resection). It does not increase treatment-related morbidity and mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.
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Affiliation(s)
- Yi Liao
- Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Abstract
Gastric adenocarcinoma is one of the most common causes of death worldwide. Surgical resection remains the mainstay of therapy, offering the only chance for complete cure. Resection is based on the principles of obtaining adequate margins, with the extent of lymphadenectomy remaining controversial. Neoadjuvant and adjuvant therapies are used to reduce local recurrence and improve long-term survival. This article reviews the literature and provides a summary of surgical management options and neoadjuvant/adjuvant therapies for gastric adenocarcinoma.
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Affiliation(s)
- Sameer H Patel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, Northeast 2nd Floor, Atlanta, GA 30322, USA
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Chen XZ, Yang K, Liu J, Chen XL, Hu JK. Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer. World J Gastroenterol 2011; 17:4542-4544. [PMID: 22110287 PMCID: PMC3218147 DOI: 10.3748/wjg.v17.i40.4542] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2011] [Revised: 04/03/2011] [Accepted: 04/10/2011] [Indexed: 02/06/2023] Open
Abstract
Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemotherapy (AC), while control was surgery alone. The results showed that NAC plus surgery did not benefit the patients with locally AGC in their overall survival [odds ratio (OR) = 1.20, 95% CI 0.80-1.80, P = 0.37] and the number needed to treat (NNT) was 74. However, the NAC plus both surgery and AC had a slight overall survival benefit (OR = 1.33, 95% CI 1.03-1.71, P = 0.03) and NNT was 14, which is superior to the NAC plus surgery. Therefore, we recommend that combined NAC and AC should be used to improve the overall survival of the locally AGC patients.
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Ahn HS, Lee HJ, Yoo MW, Jeong SH, Park DJ, Kim HH, Kim WH, Lee KU, Yang HK. Changes in clinicopathological features and survival after gastrectomy for gastric cancer over a 20-year period. Br J Surg 2011; 98:255-60. [PMID: 21082693 DOI: 10.1002/bjs.7310] [Citation(s) in RCA: 162] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The pattern of gastric cancer in the Western world is changing, with an increased proportion of tumours in the upper stomach. The aim of this study was to investigate changes in clinicopathological features and survival of patients with resected gastric cancer at a single institution, in an area of high incidence in the Far East. METHODS Clinical features and pathological findings were compared in patients with gastric cancer who underwent gastrectomy at Seoul National University Hospital during four consecutive periods (1986-1990, 1991-1995, 1996-2000 and 2001-2006). RESULTS There were 12 026 patients. The mean age increased from 53·4 years in the first period to 57·4 years in the last (P < 0·001). The proportion of patients aged 70 years or older also increased, reaching 16·1 per cent in the final period. Upper-third cancer increased from 5·3 per cent in the first period to 14·0 per cent in the fourth (P < 0·001). Early gastric cancer (pathological T1) increased continuously over the four time intervals, from 24·8 to 48·9 per cent (P < 0·001). The overall 5-year survival rate increased from 64·0 per cent in the first period to 73·2 per cent at the end (P < 0·001), and this survival improvement was apparent in patients aged 40 years or more. CONCLUSION The mean age of patients with gastric cancer has increased during the past 20 years. The proportion of early gastric cancer and overall survival have gradually increased, especially in patients aged over 40 years.
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Affiliation(s)
- H S Ahn
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Abstract
AIM: To study the value of neoadjuvant chemotherapy (NAC) for advanced gastric cancer by performing a meta-analysis of the published studies.
METHODS: All published controlled trials of NAC for advanced gastric cancer vs no therapy before surgery were searched. Studies that included patients with metastases at enrollment were excluded. Databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, and American Society of Clinical Oncology meeting abstracts from 1978 to 2010. The censor date was up to April 2010. Primary outcome was the odds ratio (OR) for improving overall survival rate of patients with advanced gastric cancer. Secondary outcome was the OR for down-staging tumor and increasing R0 resection in patients with advanced gastric cancer. Safety analyses were also performed. All calculations and statistical tests were performed using RevMan 5.0 software.
RESULTS: A total of 2271 patients with advanced gastric cancer enrolled in 14 trials were divided into NAC group (n = 1054) and control group (n = 1217). The patients were followed up for a median time of 54 mo. NAC significantly improved the survival rate [OR = 1.27, 95% confidence interval (CI): 1.04-1.55], tumor stage (OR = 1.71, 95% CI: 1.26-2.33) and R0 resection rate (OR = 1.51, 95% CI: 1.19-1.91) of patients with advanced gastric cancer. No obvious safety concerns were raised in these trials.
CONCLUSION: NAC can improve tumor stage and survival rate of patients with advanced gastric cancer with a rather good safety.
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Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer. Gastric Cancer 2010; 13:101-8. [PMID: 20602197 DOI: 10.1007/s10120-010-0547-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2009] [Accepted: 02/10/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND This pilot study was carried out to evaluate the efficacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy. METHODS Sixteen patients were enrolled. Paclitaxel was administered at 120 mg/m(2) on day 1 and S-1 was administered orally at 80 mg/m(2) for 14 consecutive days, followed by a 1-week rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefit. RESULTS Partial response or stable disease with clinical benefit was confirmed in seven and five patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% (6 cases) at surgery. The median survival time was 555 days. Leucopenia of grade 3 and neutropenia of grade 3 were recognized in two and three patients, respectively. CONCLUSION This chemotherapy regimen may be an acceptable option for patients with peritoneal dissemination. We plan to study this regimen further in gastric cancer patients with peritoneal dissemination.
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Gastric cancer. Crit Rev Oncol Hematol 2009; 71:127-64. [PMID: 19230702 DOI: 10.1016/j.critrevonc.2009.01.004] [Citation(s) in RCA: 323] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Revised: 01/08/2009] [Accepted: 01/15/2009] [Indexed: 02/08/2023] Open
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Tamura S, Miki H, Okada K, Miyake T, Yoshimura M, Suzuki R, Nakahira S, Nakata K, Okamura S, Sugimoto K, Takatsuka Y. Pilot study of intraperitoneal administration of paclitaxel and oral S-1 for patients with peritoneal metastasis due to advanced gastric cancer. Int J Clin Oncol 2008; 13:536-40. [PMID: 19093182 DOI: 10.1007/s10147-008-0836-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2007] [Accepted: 04/10/2008] [Indexed: 11/30/2022]
Abstract
BACKGROUND There is no standard treatment for peritoneal dissemination from gastric cancer. A novel combination chemotherapy has been introduced for patients with advanced gastric cancer with peritoneal metastasis. METHODS This pilot study was performed on four patients to confirm safety and efficacy. They were diagnosed with unresectable gastric cancer with severe peritoneal dissemination by staging laparoscopy, or with metastasis to the transverse colon. We selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m(2) or 60 mg/body was administered intraperitoneally on days 1 and 8 and S-1, at 80-120 mg/body, was administered orally for 14 days followed by 7 days' rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated by conventional examinations, and second-look laparoscopy was performed to assess the efficacy of the treatment against the peritoneal metastases. RESULTS After five courses, primary tumor reductions were confirmed, and no cancer cells were detected on pathocytological investigation during second-look laparoscopy in any of the patients. Three patients underwent total gastrectomy with lymph node dissection and one underwent left upper abdominal evisceration. Final histological staging showed two stage 3 and two stage 4 patients. The intraperitoneal administration of paclitaxel and the oral administration of S-1 were well tolerated. Three patients died, at 8, 15, and 29 months, respectively, after the initial treatment, and one has been alive for 54 months without recurrence. CONCLUSION This chemotherapy can be used in the treatment of patients with peritoneal metastasis of gastric cancer.
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Affiliation(s)
- Shigeyuki Tamura
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, 660-8511, Japan.
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Tamura S, Miki H, Nakata K, Takiuchi D, Okada K, Nakahira S, Okamura S, Sugimoto K, Tomita N, Takatsuka Y. Intraperitoneal administration of paclitaxel and oral S-1 for a patient with peritoneal dissemination and hydronephrosis due to advanced gastric cancer. Gastric Cancer 2008; 10:251-5. [PMID: 18095081 DOI: 10.1007/s10120-007-0431-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2007] [Accepted: 06/25/2007] [Indexed: 02/07/2023]
Abstract
We report a patient with type 3 gastric cancer with peritoneal dissemination and hydronephrosis who was successfully treated with intraperitoneal infusion of paclitaxel and oral administration of S-1. He was diagnosed with unresectable gastric cancer with severe peritoneal dissemination by staging laparoscopy. We selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m(2) was administered intraperitoneally on days 1 and 8, and S-1 at 100 mg/body was administered orally for 14 days, followed by 7 days' rest, as one course. After five courses, primary tumor reduction was confirmed and no cancer cells were detected on pathocytological investigation at second-look laparoscopy. The patient underwent total gastrectomy with lymph node dissection. He died from liver metastasis 29 months after the initial treatment, but he had not suffered from peritoneal metastases and had kept a good quality of life (QOL) since that treatment. This chemotherapy can be applied as one of the promising candidates for the treatment of patients with peritoneal metastasis of gastric cancer.
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Affiliation(s)
- Shigeyuki Tamura
- Department of Surgery, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, 660-8511, Japan
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Abstract
Although gastric cancer is still a worldwide major public health concern, it remains relatively uncommon in the Western countries. Despite improvement in surgical morbidity and mortality, as well as significant advancement of chemotherapy and radiotherapy options, the survival for gastric cancer has not significantly improved over the past decades. In the United States, standard of care for localized resectable gastric cancer is with adjuvant chemoradiotherapy. In this article, we summarize salient randomized and phase II and III clinical trials representing current treatment for gastric cancer.
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Affiliation(s)
- Alexandria T Phan
- University of Texas MD Anderson Cancer Center, GI Medical Oncology Department, 1515 Holcombe Boulevard, Mailbox 426, Houston, TX 77030, USA.
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Wu AW, Xu GW, Wang HY, Ji JF, Tang JL. WITHDRAWN: Neoadjuvant chemotherapy versus none for resectable gastric cancer. Cochrane Database Syst Rev 2007; 2007:CD005047. [PMID: 17943834 PMCID: PMC10658827 DOI: 10.1002/14651858.cd005047.pub3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Gastric cancer is a major cause of cancer death, and many patients are only diagnosed when the cancer has reached an advanced stage. Neoadjuvant chemotherapy (NAC), that is, chemotherapy administered shortly before surgical treatment, could provide a method of increasing the possibility of complete resection and survival. OBJECTIVES To evaluate the effect of neoadjuvant chemotherapy versus none for patients with resectable gastric cancer in terms of efficacy and toxicity. SEARCH STRATEGY Electronic databases including Cochrane Library, MEDLINE, EMBASE, CancerLit, Chinese Biomedical Literature Database (CBMDISC) and ongoing clinical trials as well as handsearching of conference proceedings, were searched to retrieve relevant data. SELECTION CRITERIA Randomized controlled clinical trials of neoadjuvant chemotherapy on resectable gastric cancer. DATA COLLECTION AND ANALYSIS We identified a total of 36 published citations or meeting abstracts. Thirty-two items were excluded. Of the four remaining studies, three stated random allocation but the method of randomization was unclear. Two of these employed allocation concealment by sealed envelope which was controlled by an independent party. None of the trials was double blind. All trials presented a detailed description of the number of withdrawals, dropouts and losses to follow-up. MAIN RESULTS Of the four clinical trials enrolled, there were 250 and 332 cases in total, with 106 and 126 deaths at the end of follow-up in the NAC and control group, respectively. The OR (odds ratio) was 1.05 (95%CI: 0.73-1.50), which was not statistically significant. Of the evaluable 129 patients receiving NAC, 28.7% demonstrated either a complete or a partial response. Two studies of NAC in resectable gastric cancer had resection rate data available for analysis The R0 resection rate in the NAC group was comparable to that in the control (OR: 0.96 (95%CI: 0.51-1.83)). The morbidity and mortality of NAC varied with the regimens used preoperatively. Of the 129 patients included in the analyzed studies, some acceptable toxicity was observed. AUTHORS' CONCLUSIONS There is no definite evidence of the effectiveness of NAC in resectable gastric cancer, in terms of improvements in patient survival, in the trials we reviewed. Neoadjuvant chemotherapy should not be used routinely in clinical setting until further results from randomized clinical are available. Neoadjuvant chemotherapy of gastric cancer should be applied under the framework of clinical trials.
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Affiliation(s)
- A W Wu
- Peking University, Surgical Oncology, Fucheng Road, No.52, Haidian District, Beijing, China, 100036.
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Song KY, Kim JJ, Kim SN, Park CH. Staging laparoscopy for advanced gastric cancer: is it also useful for the group which has an aggressive surgical strategy? World J Surg 2007; 31:1228-3. [PMID: 17464538 DOI: 10.1007/s00268-007-9017-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Staging laparoscopy has been shown to be useful for increasing the accuracy of preoperative staging. However, controversy still exists regarding patient selection and subsequent treatment. The aim of this study was to determine the role of staging laparoscopy for a group that has a policy to perform aggressive surgery for advanced gastric cancer. METHODS Twenty-four patients with clinical T3 or T4 gastric cancer expected to undergo curative resection, based on conventional preoperative diagnostic methods underwent staging laparoscopy. We examined the accuracy and the impact of staging laparoscopy on the further treatment options. RESULTS The mean running time for the staging laparoscopy was 40.7 min (range: 25-75 min), and one complication was noted (4.2%). In regard to the tumor depth, 11 of 24 (45.8%) cases had a discrepancy after staging laparoscopy. In addition, 15 of 24 patients (62.5%) were found to have unsuspected peritoneal metastases, and 8 patients (33.3%) were excluded from laparotomy. The remaining 16 patients (66.7%), including 9 patients with localized peritoneal metastases (P1), underwent resection. The diagnostic accuracy for T factor was 81.3% in 16 laparotomy cases and overall accuracy of P factor was 91.7%. CONCLUSIONS Staging laparoscopy had a significant impact on decisions regarding the treatment plan in patients with advanced gastric cancer for a group that has an aggressive treatment strategy.
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Affiliation(s)
- Kyo Young Song
- Department of Surgery, The Catholic University of Korea, Kangnam St. Mary's Hospital. 505 Banpo-dong, Seocho-gu, Seoul, Korea
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Wu AW, Xu GW, Wang HY, Ji JF, Tang JL. Neoadjuvant chemotherapy versus none for resectable gastric cancer. Cochrane Database Syst Rev 2007:CD005047. [PMID: 17443566 DOI: 10.1002/14651858.cd005047.pub2] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Gastric cancer is a major cause of cancer death, and many patients are only diagnosed when the cancer has reached an advanced stage. Neoadjuvant chemotherapy (NAC), that is, chemotherapy administered shortly before surgical treatment, could provide a method of increasing the possibility of complete resection and survival. OBJECTIVES To evaluate the effect of neoadjuvant chemotherapy versus none for patients with resectable gastric cancer in terms of efficacy and toxicity. SEARCH STRATEGY Electronic databases including Cochrane Library, MEDLINE, EMBASE, CancerLit, Chinese Biomedical Literature Database (CBMDISC) and ongoing clinical trials as well as handsearching of conference proceedings, were searched to retrieve relevant data. SELECTION CRITERIA Randomized controlled clinical trials of neoadjuvant chemotherapy on resectable gastric cancer. DATA COLLECTION AND ANALYSIS We identified a total of 36 published citations or meeting abstracts. Thirty-two items were excluded. Of the four remaining studies, three stated random allocation but the method of randomization was unclear. Two of these employed allocation concealment by sealed envelope which was controlled by an independent party. None of the trials was double blind. All trials presented a detailed description of the number of withdrawals, dropouts and losses to follow-up. MAIN RESULTS Of the four clinical trials enrolled, there were 250 and 332 cases in total, with 106 and 126 deaths at the end of follow-up in the NAC and control group, respectively. The OR (odds ratio) was 1.05 (95%CI: 0.73-1.50), which was not statistically significant. Of the evaluable 129 patients receiving NAC, 28.7% demonstrated either a complete or a partial response. Two studies of NAC in resectable gastric cancer had resection rate data available for analysis The R0 resection rate in the NAC group was comparable to that in the control (OR: 0.96 (95%CI: 0.51-1.83)). The morbidity and mortality of NAC varied with the regimens used preoperatively. Of the 129 patients included in the analyzed studies, some acceptable toxicity was observed. AUTHORS' CONCLUSIONS There is no definite evidence of the effectiveness of NAC in resectable gastric cancer, in terms of improvements in patient survival, in the trials we reviewed. Neoadjuvant chemotherapy should not be used routinely in clinical setting until further results from randomized clinical are available. Neoadjuvant chemotherapy of gastric cancer should be applied under the framework of clinical trials.
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Affiliation(s)
- A W Wu
- Peking University, Surgical Oncology, Fucheng Road, No.52, Haidian District, Beijing, China, 100036.
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Park CH, Song KY, Kim SN. Treatment results for gastric cancer surgery: 12 years' experience at a single institute in Korea. Eur J Surg Oncol 2007; 34:36-41. [PMID: 17442532 DOI: 10.1016/j.ejso.2007.03.004] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2006] [Accepted: 03/02/2007] [Indexed: 12/12/2022] Open
Abstract
AIMS To evaluate the changing trends of clinicopathologic features, surgical procedures and treatment outcomes of gastric cancer in a large-volume center. METHODS We divided the time period into two parts: the first is 1989-1996 (period I) and the second is 1997-2001 (period II). Then we analyzed prospectively collected data on 1816 patients treated at Kangnam St. Mary's Hospital, The Catholic University of Korea, from 1989 to 2001. RESULTS Upper one-third cancer was seen more prevalently in period II than period I (9.4% versus 6.6%) (p=0.000) and total gastrectomy was performed more frequently in period II than period I (25% versus 18%) (p=0.000). A diagnosis of early gastric cancer was made more prevalently in period II than period I (40% versus 27%) (p=0.000). D2 lymphadenectomy was done in 74% of the period I patients and 83% of their period II counterparts (p=0.000). Between the two periods, there was a significant difference in the incidence of operation-related major complications (9.9% in period I versus 3.9% in period II) (p=0.000) and the mortality (1.8% versus 0.6%) (p=0.023). The overall 5-year and 10-year survival rates were significantly higher in period II than period I (63% and 57% in period I versus 69% and 64% in period II) (p=0.009). CONCLUSIONS The overall survival of gastric cancer significantly increased because of the early detection and aggressive surgical approaches by experienced surgeons in a large-volume center. More effective multidisciplinary approaches are warranted to improve the prognosis of advanced gastric cancer.
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Affiliation(s)
- C H Park
- Department of Surgery, College of Medicine, The Catholic University of Korea, Kangnam St. Mary's Hospital, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
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Satoh S, Hasegawa S, Ozaki N, Okabe H, Watanabe G, Nagayama S, Fukushima M, Takabayashi A, Sakai Y. Retrospective analysis of 45 consecutive patients with advanced gastric cancer treated with neoadjuvant chemotherapy using an S-1/CDDP combination. Gastric Cancer 2006; 9:129-35. [PMID: 16767369 DOI: 10.1007/s10120-006-0369-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2005] [Accepted: 02/14/2006] [Indexed: 02/07/2023]
Abstract
BACKGROUND Standard treatment for highly advanced gastric cancer (AGC) has not been established yet. Neoadjuvant chemotherapy (NAC) represents a promising approach, which may improve the prognosis of AGC. In this study, we analyzed the feasibility and efficacy of NAC with S-1 (TS-1)/cisplatin CDDP in order to design appropriate clinical trials for AGC. METHODS Results for a series of 45 consecutive patients with AGC treated with S-1/CDDP induction chemotherapy since January 2002 were analyzed retrospectively. RESULTS The primary tumor was resected in 36 of the 45 patients (resectability, 80.0%). Progression of the disease during chemotherapy was observed in 1 patient only (2.2%). No treatment-related deaths occurred, and serious adverse effects (grade 3-4) were noted in only 2.2% of the patients. The overall median survival time was 1.82 years. Especially noteworthy is that, in patients with highly advanced disease (pretreatment [c]-stage IV; n = 27), resectability was 66.7% and curative (R0) resection was possible in 10 patients. The median survival times for c-stage IV patients who had total, curative, and noncurative resections were 20.8, 22.3 and 12.6 months, respectively. R0 resection was possible for all c-stage III patients (n = 17), with a 2-year overall survival of 90.9%. The downstaging rate was 55.6% (20/36), resulting in a significantly improved prognosis for the downstaged patients (P = 0.012). CONCLUSION Induction chemotherapy using S-1/CDDP for AGC appears to be a safe and promising treatment. We have therefore started two independent multiinstitutional clinical trials to evaluate the efficacy of this treatment.
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Affiliation(s)
- Seiji Satoh
- Department of Surgery, Kyoto University Hospital, Kyoto 606-8507, Japan
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Nonaka T, Nishibashi K, Itoh Y, Yana I, Seiki M. Competitive disruption of the tumor-promoting function of membrane type 1 matrix metalloproteinase/matrix metalloproteinase-14 in vivo. Mol Cancer Ther 2005; 4:1157-66. [PMID: 16093431 DOI: 10.1158/1535-7163.mct-05-0127] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Membrane type 1 matrix metalloproteinase (MT1-MMP) is a potent modulator of the pericellular environment and promotes tumor cell invasion and proliferation in many types of tumor. The activation of proMMP-2 and processing of collagen I by MT1-MMP have been thought to be important for its tumor-promoting function. These activities can be inhibited by mutant forms of MT1-MMP lacking the catalytic domain. However, the effect of such dominant-negative mutants has never been evaluated in vivo. Various mutants lacking the catalytic domain (dCAT) were prepared and confirmed to inhibit MT1-MMP activity in human fibrosarcoma HT1080 cells, and tumor cells expressing these mutants were implanted s.c. into nude mice to monitor tumor formation. Only the membrane-anchored form of a dCAT construct through the transmembrane domain [dCAT(1)] showed potent antitumor activity not only in HT1080 cells but also in gastric carcinoma MKN28 and MKN45 cells expressing MT1-MMP. A soluble form of dCAT lacking the transmembrane domain did not show such activity. The expression of dCAT(1) in MKN28 or MKN45 further prevented the metastatic spread of tumor cells into the peritoneal cavity; however, dCAT(1) showed no effect against TMK-1, another gastric carcinoma cell line expressing no MT1-MMP. It is of note that the tumorigenicity of TMK-1 cells enhanced by MT1-MMP overexpression was, in turn, canceled by the additional expression of dCAT(1). Thus, MT1-MMP expressed in tumor cells seems to play a pivotal role in tumor growth in mice. The results also suggest new possibilities to abrogate the tumor-promoting function of MT1-MMP other than the conventional protease inhibitor-based approach.
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Affiliation(s)
- Takahiro Nonaka
- Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato, Tokyo 108-8639, Japan
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Abstract
Although the incidence of gastric cancer is decreasing, it remains a significant source of cancer-related mortality. Surgery remains the best chance for cure from gastric cancer. Adjuvant and neoadjuvant therapy have played increasing roles in attempting to reduce the disease-specific mortality and prolong survival. In this article, the authors review the literature and summarize the salient points regarding the roles of adjuvant and neoadjuvant therapy for gastric cancer.
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Affiliation(s)
- Ricardo J Gonzalez
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Unit 444, 1515 Holcombe Boulevard, Houston, TX 77030-5235, USA
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Abstract
Gastric cancer is one of the most common cancers and one of the most frequent causes of cancer-related deaths. The incidence, diagnostic studies, and therapeutic options have undergone important changes in the last decades, but the prognosis for gastric cancer patients remains poor, especially in more advanced stages. Surgery is the mainstay of treatment of this disease, even if it is associated with a high rate of locoregional and distant recurrence. There is ongoing debate regarding the role of adjuvant treatment In advanced disease, palliation of symptoms, rather than cure, is the primary goal of patient management. Several combination therapies have been developed and have been examined in phase III trials; however, in most cases, they have failed to demonstrate a survival advantage over the reference arm. This review summarizes the most important recommendations for the management of patients with gastric cancer.
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Abstract
Neoadjuvant therapy, an adjunctive therapy given before the main therapy, has become an integral part of modem multidisciplinary cancer management. Organized by the primary organ involved by cancer, this review summarizes the outcomes of neoadjuvant therapy for common malignant solid tumors, based on large, randomized, controlled trials. In locally advanced rectal, laryngeal, and breast cancer, neoadjuvant therapy enables organ preservation; however, it does not improve overall survival when compared with definitive treatment followed by adjuvant therapy. In locally advanced bladder and cervical cancer, patients who undergo neoadjuvant therapy before radical surgery appear to have better survival than those receiving definitive therapy alone; however, it is unclear if the neoadjuvant approach will be superior to definitive therapy followed by adjuvant therapy. To date, the survival benefits of neoadjuvant therapy for resectable non-small cell lung, esophageal, gastric, and prostate cancer remains under investigation.
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Affiliation(s)
- Tawee Tanvetyanon
- Division of Hematology/Oncology, Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA.
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Prognostic indicators in locally advanced gastric cancer (LAGC) treated with preoperative chemotherapy and D2-gastrectomy. J Surg Oncol 2005; 89:227-36; discussion 237-8. [PMID: 15726615 DOI: 10.1002/jso.20207] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Neoadjuvant chemotherapy is increasingly considered an effective treatment option for patients with gastric carcinoma. Aim of the study is to evaluate the prognostic significance of the pathological response and of known prognostic factors in a group of accurately staged locally advanced gastric cancer (LAGC) patients. METHODS Thirty-three patients with LAGC, staged by laparoscopy, underwent D2-gastrectomy after preoperative chemotherapy. Survival was calculated by Kaplan-Meier method and differences were assessed by the Log-rank and Breslow test. Multivariate analysis was performed using the Cox proportional hazard model in backward stepwise regression. RESULTS Curative resection (R0) was achieved in 81.8% of patients. A complete or subtotal pathological response was documented in 3 and 6%, respectively. Nineteen out of thirty-three (57.6%) patients were alive and 16 of them were free of relapse at last follow-up. Survival rates were 81, 67, and 59% at 12, 24, and 36 months, respectively. At univariate and multivariate analysis, only R0 resection was found to be an independent prognostic factor. CONCLUSIONS In the current study, R0 resection is the most important prognostic factor for resectable LAGC; according to our results we feel encouraged to consider neoadjuvant chemotherapy a promising modality for increasing the R0-percentage of gastric carcinoma patients who could benefit from a curative surgery.
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Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg 2005; 241:27-39. [PMID: 15621988 PMCID: PMC1356843 DOI: 10.1097/01.sla.0000149300.28588.23] [Citation(s) in RCA: 501] [Impact Index Per Article: 25.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE This update reviews the epidemiology and surgical management, and the controversies of gastric adenocarcinoma. We provide the relevance of outcome data to surgical decision-making and discuss the application of gene-expression analysis to clinical practice. SUMMARY BACKGROUND DATA Gastric cancer mortality rates have remained relatively unchanged over the past 30 years, and gastric cancer continues to be one of the leading causes of cancer-related death. Well-conducted studies have stimulated changes to surgical decision-making and technique. Microarray studies linked to predictive outcome models are poised to advance our understanding of the biologic behavior of gastric cancer and improve surgical management and outcome. METHODS We performed a review of the English gastric adenocarcinoma medical literature (1980-2003). This review included epidemiology, pathology and staging, surgical management, issues and controversies in management, prognostic variables, and the application of outcome models to gastric cancer. The results of DNA microarray analysis in various cancers and its predictive abilities in gastric cancer are considered. RESULTS Prognostic studies have provided valuable data to better the understanding of gastric cancer. These studies have contributed to improved surgical technique, more accurate pathologic characterization, and the identification of clinically useful prognostic markers. The application of microarray analysis linked to predictive models will provide a molecular understanding of the biology driving gastric cancer. CONCLUSIONS Predictive models generate important information allowing a logical evolution in the surgical and pathologic understanding and therapy for gastric cancer. However, a greater understanding of the molecular changes associated with gastric cancer is needed to guide surgical and medical therapy.
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Affiliation(s)
- Bryan J Dicken
- Department of Surgery, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
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Yao JC, Mansfield PF, Pisters PWT, Feig BW, Janjan NA, Crane C, Ajani JA. Combined-modality therapy for gastric cancer. ACTA ACUST UNITED AC 2004; 21:223-7. [PMID: 14648779 DOI: 10.1002/ssu.10040] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Gastric cancer has a poor prognosis. It is often diagnosed at an advanced stage, and potentially curative treatments often can not be exercised. Even when a curative surgical resection is possible, only a minority of patients survive beyond 5 years, and locoregional failures are frequent among patients undergoing curative resections. Recently, the use of postoperative adjuvant chemoradiotherapy has yielded some notable benefits. Earlier studies have shown survival benefits in patients undergoing chemoradiotherapy for locally advanced unresectable gastric cancer. The recently reported Intergroup 0116 trial compared surgery alone with surgery plus postoperative chemotherapy plus chemoradiotherapy. Superior overall and disease-free survival rates among patients given combined-modality postoperative therapy were observed. These results established a new standard of care for patients following resection of gastric carcinoma. Preoperative combined-modality chemoradiotherapy may improve resectability, and is under investigation at the University of Texas M. D. Anderson Cancer Center. The development of novel radioenhancers and the selection of therapy on the basis of molecular determinants of response may result in much-needed advances in this field.
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Affiliation(s)
- James C Yao
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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Aparicio T, Yacoub M, Karila-Cohen P, René E. Adénocarcinome gastrique : notions fondamentales, diagnostic et traitement. EMC - CHIRURGIE 2004; 1:47-66. [DOI: 10.1016/j.emcchi.2003.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Tsujitani S, Fukuda K, Kaibara N. Combination chemotherapy of S-1 and low-dose cisplatin for advanced gastric cancer. Gastric Cancer 2003; 6 Suppl 1:50-7. [PMID: 12775021 DOI: 10.1007/s10120-003-0223-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND A previous phase II study showed that S-1 (TS-1) was effective for advanced gastric cancers and had mild toxicity. The present study aimed to evaluate the efficacy and feasibility of this novel anticancer drug combined with low-dose cisplatin (CDDP). METHODS Fifteen patients with unresectable and recurrent gastric cancer were enrolled. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2 per day according to the late phase II trial protocol. One course consisted of 28 days' consecutive administration followed by 14 days' rest. Five or 10 mg CDDP was infused three times each week (days 1, 3, 5) during S-1 administration on hospitalization, and once each week (day 1) at the outpatient clinic. Patients' backgrounds, response rates, response durations, and time to progression were investigated. RESULTS None of the 15 patients had a complete response and 8 had a partial response. Therefore, the overall response rate was 53% (8/15). For site efficacy, the response rate was 50% (5/10) for the primary lesion, 50% (3/6) for liver metastasis, and 39% (5/13) for lymph node metastasis. The median response duration of the 8 responders was 4 months, and the time to progression was 3.3 months. Adverse reactions appeared in 60% (9/15). The incidence of adverse reactions of grades 3 and 4 was 13% (2/15) and 0%, respectively. As for hematological toxicity, grade 3 leukopenia was observed in 2 patients (2/15), but decreased hemoglobin level and thrombocytopenia did not appear. Although gastrointestinal adverse reactions appeared in 40% (6/15), all reactions were grades 1 and 2. Because of the mild toxicity, most patients were treated at the outpatient clinic. CONCLUSIONS Combination chemotherapy of S-1 and low-dose CDDP is expected to be a useful chemotherapy for advanced gastric cancer.
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Affiliation(s)
- Shunichi Tsujitani
- Department of Surgery, Division of Surgical Oncology, School of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan
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Janunger KG, Hafström L, Glimelius B. Chemotherapy in gastric cancer: a review and updated meta-analysis. THE EUROPEAN JOURNAL OF SURGERY = ACTA CHIRURGICA 2003; 168:597-608. [PMID: 12699095 DOI: 10.1080/11024150201680005] [Citation(s) in RCA: 175] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED The five years survival rate for patients with gastric cancer is 15-25%. With the aim of improving survival, chemotherapy has been used in different adjuvant settings. Similarly, but with the aim of improving quality of life and prolonging life, chemotherapy has been used extensively in metastatic disease. In this review we have included studies of systemic and intraperitoneal chemotherapy given before, during or after operation and for advanced disease. A meta-analysis has been made on the 21 randomised studies that used adjuvant systemic chemotherapy postoperatively. A significant survival benefit for the patients treated postoperatively compared with controls was identified (odds ratio (OR) 0.84, 95% confidence interval (CI) 0.74 to 0.96). When western and Asian studies were analysed separately we found no survival benefit for the treated patients in the western groups (OR 0.96 (95 CI 0.83 to 1.12)). Flaws in the conduct of several trials made it difficult to draw firm conclusions, including the exclusion of a small but clinically meaningful survival benefit. Preoperative or neoadjuvant chemotherapy has shown effects in some patients, but no significant benefit was found in the few randomised studies. The few studies that reported intraperitoneal therapy showed no detectable survival benefit either. In patients with advanced disease, four small randomised studies found significantly longer survival in the treated patients. The survival benefit is in the range of 3-9 months, and there were also improvements of the quality of life. Several drug combinations have been tested, however, with no confirmed superiority for a particular regimen. CONCLUSIONS Adjuvant chemotherapy cannot be recommended as a routine because of the lack of confirmed beneficial effects. Some patients with advanced disease will have a clinically important benefit from palliative chemotherapy, so this can be recommended for patients who are otherwise in good health.
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Affiliation(s)
- Karl-Gunnar Janunger
- Department of Surgical and Perioperative Sciences--Surgery, University Hospital, Umeå, Sweden.
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Menges M, Schmidt C, Lindemann W, Ridwelski K, Pueschel W, Jüngling B, Feifel G, Schilling M, Stallmach A, Zeitz M. Low toxic neoadjuvant cisplatin, 5-fluorouracil and folinic acid in locally advanced gastric cancer yields high R-0 resection rate. J Cancer Res Clin Oncol 2003; 129:423-9. [PMID: 12836016 DOI: 10.1007/s00432-003-0467-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2003] [Accepted: 05/23/2003] [Indexed: 01/29/2023]
Abstract
PURPOSE Neoadjuvant chemotherapy in locally advanced gastric cancer is effective, but is often associated with severe side effects, including fatal outcome. This study evaluates a combination of cisplatin, folinic acid and 5-fluorouracil (PLF) in terms of efficacy (R-0 resection rate) and toxicity. METHODS Twenty-five patients with locally advanced gastric cancer who after extensive staging were deemed not suitable for curative resection underwent neoadjuvant chemotherapy. Three or four cycles of cisplatin (50 mg/m(2) days 1 and 15), folinic acid (200 mg/m(2) days 1, 8, 15 and 22), and 5-fluorouracil (2,000 mg/m(2 ) days 1, 8, 15 and 22) were administered. Cases with progressive disease were taken off the study. Two weeks after finishing chemotherapy resection was performed and all patients were enrolled in a structured follow-up. RESULTS Of the patients, 22/25 finished chemotherapy and 20 of those underwent laparotomy. In 13/25 patients (52%) a R-0 resection and in three cases a R-1 resection were achieved. Four patients stayed irresectable. During 76 completed cycles of chemotherapy we observed five cases of WHO grade-III toxicity and no grade-IV toxicity. CONCLUSIONS The presented PLF protocol yields R-0 resection rates comparable to protocols like EAP (etoposide, adriamycin, platinum), but with a better safety profile allowing administration in an outpatient setting. Our study supports PLF as a reference neoadjuvant treatment for gastric cancer even outside of clinical studies.
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Affiliation(s)
- Markus Menges
- Department of Internal Medicine II, Saarland University, 66421, Homburg, Germany.
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Yao JC, Ajani JA. Therapy of localized gastric cancer: preoperative and postoperative approaches. Ann Oncol 2003; 13 Suppl 4:7-12. [PMID: 12401660 DOI: 10.1093/annonc/mdf632] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- J C Yao
- Department of Gastrointestinal Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
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Hu JK, Chen ZX, Zhou ZG, Zhang B, Tian J, Chen JP, Wang L, Wang CH, Chen HY, Li YP. Intravenous chemotherapy for resected gastric cancer: meta-analysis of randomized controlled trials. World J Gastroenterol 2002; 8:1023-8. [PMID: 12439918 PMCID: PMC4656373 DOI: 10.3748/wjg.v8.i6.1023] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the safety and efficacy of different intravenous chemotherapeutic regimens in patients with gastric carcinomas who had undergone gastrectomy.
METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. Language was restricted to Chinese and English. RCTs were identified from Medline and Embase (1980-2001/4), and Chinese Bio-medicine Database (1990-2001/1). Literature references were checked at the same time. We included randomized and quasi-randomized trials comparing the efficacy of intravenous chemotherapy after gastrectomy with that of surgery alone in patients with confirmed gastric carcinomas who had undergone gastrectomy. Selection criteria were: randomized or quasi-randomized trials with following-up results; Trials could be double-blind, single-blind or not blind; Chemotherapy groups were given intravenous chemotherapy after gastrectomy without neo-adjuvant chemotherapy, intraperitoneal hyperthermic perfusion, radiotherapy or chemoimmunotherapy; Controlled group included those receiving gastrectomy alone. The following data were extracted: the number of survival and death by the end of the follow-up; the different agents and doses of the intravenous chemotherapy; the baseline of the chemotherapy group and the controlled arm; the serious adverse events; the statistical consideration; cost-effectiveness analysis. The statistical analysis was performed by RevMan4.1 software which was provided by the Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. Meta-analysis was done with random effects model. Heterogeneity was checked by chi-square test. Sensitivity analysis was performed by excluding the trials in which Jadad-scale was only 1 score. The result was expressed with odds ratio (OR) for the categorical variable.
RESULTS: Fourteen trials involving 4543 patients were included. Meta-analysis was done with random effects model Heterogeneity and sensitivity analysis were performed also. The effect of intravenous chemotherapy after gastrectomy was better than surgery alone (odds ratio 0.56, 95%CI 0.40-0.79). There was a significant difference between the two groups by u-test (P = 0.0008). Sensitivity analysis revealed the same difference (odds ratio 0.81, 95%CI 0.70-0.94). Of fourteen trials, only three studies were of high quality according to the Jadad-scale (with three score). There was one meta-analysis trial and the others, about ten trials, were of low quality. There was no trial which mentioned sample-size calculation, allocation concealment, intention-to-treat analysis. Most of the trials didn’t describe the blind-procedure. There were five trials which detailed the side-effects according to the toxicity grade by WHO standard. The side-effects halting treatment were haematologic and biochemical toxicity, debilitating nausea and vomiting. There were two patients died of chemotherapy toxicity.
CONCLUSION: Based on the review, intravenous chemotherapy after gastrectomy may have positive treatment effect on gastric cancer. However, the evidence is not strong because of the general low methodologic quality of the RCTs. Therefore, we can’t make the conclusion that intravenous chemotherapy after gastrectomy may have better treatment effect on gastric cancer than that of surgery alone. Rigorously designed, randomised, double-blind, placebo-controlled trials are required.
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Affiliation(s)
- Jian-Kun Hu
- General Surgery Department, West China Hospital of SiChuan University, Chengdu 610041, Sichuan Province, China.
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Nitti D, Belluco C, Mammano E, Marchet A, Ambrosi A, Mencarelli R, Segato P, Lise M. Low level of p27(Kip1) protein expression in gastric adenocarcinoma is associated with disease progression and poor outcome. J Surg Oncol 2002; 81:167-75; discussion 175-6. [PMID: 12451619 DOI: 10.1002/jso.10172] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Low tumor expression of the p27(Kip1) protein, which is involved in cell cycle control and apoptosis, is considered a negative prognostic factor in different types of cancer. The aim of this study was to evaluate the clinical and pathological significance of low p27(Kip1) protein expression in patients who had undergone resection for gastric adenocarcinoma. METHODS p27(Kip1) protein was studied by immunohistochemistry in formalin-fixed tumor sections from 95 patients who underwent resection for gastric adenocarcinoma between 1991 and 1996. Based on the median value of protein expression, p27(Kip1) protein expression was classified as low or high. RESULTS Low p27(Kip1) protein expression was significantly associated with tumor de-differentiation, increased penetration through the gastric wall, lymph node metastasis, and advanced tumor stage. In the group of 84 patients who underwent curative surgery, 5-year survival was 74% in cases with high p27(Kip1) protein expression and 38% in those with low p27(Kip1) protein expression (P < 0.001). At multivariate analysis, low p27(Kip1) protein expression was an independent negative prognostic factor for survival (RR = 3.671; P = 0.004). CONCLUSIONS In gastric adenocarcinoma, low p27(Kip1) protein expression is associated with poorly differentiated and advanced tumors and is a negative prognostic factor of potential clinical value.
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Affiliation(s)
- Donato Nitti
- Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy.
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Hribaschek A, Pross M, Kuhn R, Krüger S, Ridwelski K, Halangk W, Boltze C, Lippert H. Prevention and treatment of peritoneal carcinomatosis in experimental investigations with CPT-11 and oxaliplatin. Anticancer Drugs 2002; 13:605-14. [PMID: 12172506 DOI: 10.1097/00001813-200207000-00007] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Following surgical resection of colorectal carcinoma, local recurrence in the tumor bed or in the mesentery remains a frequently encountered problem. Currently there are no recognized standard therapy protocols for the prevention of local recurrence or the treatment of peritoneal carcinomatosis. The aim of our trial was to investigate whether CPT-11 and oxaliplatin could decrease i.p. tumor growth in a basic experimental animal model. Experiments were performed on three groups of animals plus controls. In the first group, the cytostatic agents were applied directly following tumor cell implantation into the peritoneal cavity. In the second group, early postoperative i.p. chemotherapy (days 5, 10 and 15 following surgery) was administered. In the third group, late i.p. chemotherapy (days 15, 20 and 25 after tumor cell transfer) was administered with the intention of reducing a manifest peritoneal carcinomatosis. The trial also set out to describe any side effects observed following i.p. administration. The results indicated that CPT-11 and oxaliplatin were highly effective in reducing i.p. tumor spread after direct i.p intraoperative application. Intraperitoneal administration of CPT-11 or oxaliplatin also decreased i.p. tumor growth after early i.p. chemotherapy. CPT-11 was a little more effective with lower side effects. However, it was clear that it was not possible to treat a manifest peritoneal carcinomatosis in this way.
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Affiliation(s)
- A Hribaschek
- Department of Surgery, University of Magdeburg, Leipzigerstrasse 44, Germany.
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Abstract
Standard chemotherapy for advanced gastric cancer remains undefined. Two of the most popular regimens-ECF [epirubicin-cisplatin-5-fluorouracil (5-FU)] and PELF (cisplatin-epirubicin-5-FU-leucovorin)-have been shown to be active, but each has limitations. Phase II trials show that single-agent docetaxel is an active agent in advanced gastric cancer, producing overall response rates (ORRs) of 17.5-24%. Docetaxel has also been shown to lack cross-resistance with other drugs in gastric cancer, and is likely to be at least additive to cisplatin and 5-FU. Phase II results of docetaxel combinations in advanced gastric cancer are encouraging. Docetaxel-cisplatin has yielded response rates similar to those achieved by ECF and PELF. Adding 5-FU to docetaxel-cisplatin has achieved an ORR of 52 versus 45% for docetaxel-cisplatin in a randomized phase II trial. Docetaxel-based regimens demonstrate acceptable tolerability despite predictable hematotoxicity. Neutropenia, the major toxicity, is manageable by dose modification or by using prophylactic granulocyte colony stimulating factor. Several phase III trials are now ongoing, including a large-scale trial of docetaxel-cisplatin-5-FU versus cisplatin-5-FU. Results will show whether docetaxel improves overall response and survival, as suggested in the phase II setting.
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Affiliation(s)
- Daniel G Haller
- University of Pennsylvania Cancer Center, Philadelphia, PA 19104, USA
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Abstract
Gastric cancer is the second most frequently diagnosed malignancy worldwide, and the risk of relapse remains high in the majority of patients undergoing resection. Attempts to reduce this risk and prolong survival have led to numerous adjuvant chemotherapy trials that either had no benefit for patients or occasionally had controversial results. The recently reported Intergroup 0116 trial shows conclusive evidence of survival benefit for patients treated with postoperative chemoradiotherapy. In this Intergroup trial, which involves over 600 patients, a regimen of postoperative chemotherapy plus chemoradiotherapy was shown to prolong overall and disease-free survival in gastric cancer patients with stage IB through IV disease following a curative (R0) resection. This approach should be considered the standard of care in patients with gastric cancer who have undergone curative resection. Preoperative chemotherapy shows promise in downstaging tumors and increasing the rate of curative resection, but randomized trials are needed to assess survival benefits. Efforts to combine existing treatment modalities and new agents with novel mechanisms of action hold promise for the future.
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Affiliation(s)
- James C Yao
- Department of Gastrointestinal Oncology, The University of Texas M.D. Anderson Cancer Center, Box 426, 1515 Holcombe Boulevard, Houston, TX 77005-4341, USA
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