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Kuang ZY, Sun QH, Cao LC, Ma XY, Wang JX, Liu KX, Li J. Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials. World J Gastrointest Oncol 2024; 16:1046-1058. [PMID: 38577462 PMCID: PMC10989386 DOI: 10.4251/wjgo.v16.i3.1046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 01/14/2024] [Accepted: 02/04/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.
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Affiliation(s)
- Zi-Yu Kuang
- Graduate College, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
| | - Qian-Hui Sun
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Lu-Chang Cao
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xin-Yi Ma
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Jia-Xi Wang
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ke-Xin Liu
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Jie Li
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Fiflis S, Papakonstantinou M, Giakoustidis A, Christodoulidis G, Louri E, Papadopoulos VN, Giakoustidis D. Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer: A systematic review. World J Gastrointest Surg 2023; 15:1808-1818. [PMID: 37701690 PMCID: PMC10494580 DOI: 10.4240/wjgs.v15.i8.1808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/07/2023] [Accepted: 06/27/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is a major health concern worldwide. Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma, however, the optimal approach remains unclear and should be different in each individual. Chemotherapy can be administered both pre- and postoperatively, but a multidisciplinary approach is preferred when possible. This is particularly relevant for locally advanced GC (LAGC), as neoadjuvant chemotherapy (NAT) could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent. Even though the recent progress has been impressive, European and International guidelines are still controversial, thus attenuating the need for a more standardized approach in the management of locally advanced cancer. AIM To investigate the effects of NAT on the overall survival (OS), the disease-free survival (DFS), the morbidity and the mortality of patients with LAGC in comparison to upfront surgery (US). METHODS For this systematic review, a literature search was conducted between November and February 2023 in PubMed, Cochrane Library and clinicaltrials.gov for studies including patients with LAGC. Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews. RESULTS Eighteen studies with 4839 patients with LAGC in total were included in our systematic review. Patients were separated into two groups; one receiving NAT before the gastrectomy (NAT group) and the other undergoing upfront surgery (US group). The OS ranged from 41.6% to 74.2% in the NAT group and from 30.9% to 74% in the US group. The DFS was also longer in the NAT group and reached up to 80% in certain patients. The complications related to the chemotherapy or the surgery ranged from 6.4% to 38.1% in the NAT group and from 5% to 40.5% in the US group. Even though in most of the studies the morbidity was lower in the NAT group, a general conclusion could not be drawn as it seems to depend on multiple factors. Finally, regarding the mortality, the reported rate was higher and up to 5.3% in the US group. CONCLUSION NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates. However, patients with different clinicopathological features respond differently to chemotherapy, therefore currently the treatment plan should be individualized in order to achieve optimal results.
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Affiliation(s)
- Stylianos Fiflis
- A’ Department of Surgery, General Hospital Papageorgiou, Thessaloniki 56429, Greece
| | | | | | | | - Eleni Louri
- A’ Department of Surgery, General Hospital Papageorgiou, Thessaloniki 56429, Greece
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Wang Z, He T, Yu D, Qin X, Geng A, Yang H. Neoadjuvant apatinib plus tegafur/gimeracil/oteracil potassium (S‑1)/oxaliplatin chemotherapy vs. chemotherapy alone in patients with locally advanced gastric carcinoma. Exp Ther Med 2022; 24:625. [PMID: 36160880 PMCID: PMC9468841 DOI: 10.3892/etm.2022.11562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/20/2022] [Indexed: 02/03/2023] Open
Abstract
The current study aimed to evaluate the efficacy and safety of neoadjuvant apatinib plus tegafur/gimeracil/oteracil potassium (S-1) plus oxaliplatin (SOX) chemotherapy in patients with locally advanced gastric carcinoma (LAGC). Therefore, patients with LAGC treated with neoadjuvant apatinib plus SOX chemotherapy (apatinib + SOX group; n=25) or SOX chemotherapy (SOX group; n=35) were enrolled in the present study. Subsequently, the objective response (ORR) and disease control rates (DCR), pathological response, disease-free survival (DFS), overall survival (OS) and adverse events were recorded. The results showed that patients in the apatinib + SOX group exhibited a higher ORR (64.0 vs. 37.1%; P=0.040), but a similar DCR (96.0 vs. 88.6%; P=0.580), compared with those in the SOX group. The pathological response rates in patients with grade 0, 1, 2 and 3 LAGC were 0.0, 20.8, 62.5 and 16.7%, respectively, in the apatinib + SOX group, while in those treated with SOX alone they were 9.1, 39.4, 42.4 and 9.1%, respectively. By contrast, the pathological response was elevated in the apatinib + SOX group compared with the SOX group (P=0.030). During a median follow-up period of 21.0 months (range, 6.4-38.1 months), median DFS and OS were not reached. More specifically, the 1-, 2- and 3-year DFS rates were 91.7, 75.2 and 75.2% in the apatinib + SOX group and 71.8, 59.6 and 44.7% in the SOX group, respectively. In addition, the 1-, 2- and 3-year OS rates were 100.0, 89.6 and 78.4% in the apatinib + SOX group, while those in the SOX group were 90.3, 69.2 and 55.4%, respectively. However, no differences in DFS (P=0.094) or OS (P=0.155) were observed between the two groups. Additionally, the most common adverse events in the SOX group were mild leukopenia (42.9%) and fatigue (34.3%), while those in the apatinib + SOX group were tolerable leukopenia (44.0%) and hypertension (44.0%). In conclusion, the present study suggested that neoadjuvant apatinib plus SOX chemotherapy could be more effective and tolerable compared with SOX chemotherapy alone in patients with LAGC.
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Affiliation(s)
- Zhenfeng Wang
- Department of General Surgery, The Second People's Hospital of Liaocheng, Linqing, Liaocheng, Shandong 252699, P.R. China
| | - Tingbang He
- Department of General Surgery, The People's Hospital of Xiajin Affiliated to Shandong First Medical University, Xiajin, Dezhou, Shandong 253299, P.R. China
| | - Deguo Yu
- Department of Emergency Surgery, The Second People's Hospital of Liaocheng, Linqing, Liaocheng, Shandong 252699, P.R. China
| | - Xiantao Qin
- Department of General Surgery, The Second People's Hospital of Liaocheng, Linqing, Liaocheng, Shandong 252699, P.R. China
| | - Aizhi Geng
- Department of Gynecology, The Second People's Hospital of Liaocheng, Linqing, Liaocheng, Shandong 252699, P.R. China
| | - Hailei Yang
- Department of Gynecology, The Second People's Hospital of Liaocheng, Linqing, Liaocheng, Shandong 252699, P.R. China
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Feng Q, Long D, Du MS, Wang XS, Li ZS, Zhao YL, Qian F, Wen Y, Yu PW, Shi Y. Short-Term Clinical Efficacy of Neoadjuvant Chemotherapy Combined With Laparoscopic Gastrectomy for Locally Advanced Siewert Type II and III Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Propensity Score-Matched Study. Front Oncol 2021; 11:690662. [PMID: 34660265 PMCID: PMC8511681 DOI: 10.3389/fonc.2021.690662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 08/24/2021] [Indexed: 02/03/2023] Open
Abstract
Background Laparoscopic gastrectomy (LG) has been increasingly used for the treatment of locally advanced Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). However, whether LG can achieve the same short-term efficacy in the treatment of patients who receive neoadjuvant chemotherapy (NACT) remains controversial. Thus, the aim of this study was to investigate the clinical outcomes of NACT combined with LG for Siewert type II and III AEG. Methods This retrospective study identified patients with locally advanced Siewert type II and III AEG diagnosed between May 2011 and October 2020 using the clinical tumor-node-metastasis (cTNM) staging system. The short-term outcomes were compared between the matched groups using a 1:3 propensity score matching (PSM) method, which was performed to reduce bias in patient selection. Results After PSM, 164 patients were selected, including 41 in the NACT group and 123 in the LG group. The baseline characteristics were similar between the two groups. Compared with the LG group, the NACT group exhibit a smaller tumor size and significantly less advanced pathological tumor classification and nodal classification stages. The time to first flatus of the NACT group was significantly shorter, but the hospital stay was significantly longer than that of the LG group. The NACT group showed similar overall (29.3% vs 25.2%, P=0.683), systemic (24.4% vs 21.1%, P=0.663), local (12.2% vs 9.8%, P=0.767), minor (19.5% vs 19.5%, P=1.000) and major (9.8% vs 5.7%, P=0.470) complications as the LG group. Subgroup analyses showed no significant differences in most stratified parameters. Operation time≥ 300 minutes was identified as an independent risk factor for overall complications. Age≥ 60 years was identified as an independent risk factor for major complications. Conclusion NACT combined with LG for AEG does not increase the risk of postoperative morbidity and mortality compared with LG.
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Affiliation(s)
- Qing Feng
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Du Long
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Ming-Shan Du
- Radiology Department, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Xiao-Song Wang
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Zhen-Shun Li
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Yong-Liang Zhao
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Feng Qian
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Yan Wen
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Pei-Wu Yu
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Yan Shi
- Department of General Surgery, The First Affiliated Hospital, Army Medical University, Chongqing, China
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Wang KX, Cui TY, Yang XD, Wang GQ, Jiang QS, Sun H, Jiang NY, Yong XM, Shi CB, Ding YB, Chen XF, Fang YY. Study on Efficacy and Safety of Low-Dose Apatinib Combined with Camrelizumab and SOX Regimen as First-Line Treatment of Locally Advanced and Unresectable Gastric/Gastroesophageal Junction Cancer: A Protocol for an Open-Label, Dose Escalation and Extension Phase Ib Clinical Trial. Onco Targets Ther 2021; 14:4859-4865. [PMID: 34584426 PMCID: PMC8464364 DOI: 10.2147/ott.s316288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 08/02/2021] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8-11 months in the West and 13-17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. METHODS/DESIGN This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). DISCUSSION This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy. TRIAL REGISTRATION ChiCTR.gov.cn: ChiCTR2000034109.
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Affiliation(s)
- Kang-Xin Wang
- Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Ting-Yun Cui
- Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Xu-Dong Yang
- Department of General Surgery, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Guo-Qun Wang
- Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Qiu-Sheng Jiang
- Department of General Surgery, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Hui Sun
- Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Nan-Yuan Jiang
- Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Xiao-Min Yong
- Department of Radiology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Chuan-Bing Shi
- Department of Pathology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Yong-Bin Ding
- Department of General Surgery, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
| | - Xiao-Feng Chen
- Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China
| | - Yue-Yu Fang
- Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China
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Efficacy of Neoadjuvant Chemotherapy DOX and XELOX Regimens for Patients with Resectable Gastric or Gastroesophageal Junction Adenocarcinoma. Gastroenterol Res Pract 2021; 2021:5590626. [PMID: 34335737 PMCID: PMC8324337 DOI: 10.1155/2021/5590626] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 11/17/2022] Open
Abstract
Purpose This paper is aimed at comparing the short-term efficacy of the combination of docetaxel, oxaliplatin, and capecitabine (DOX) with the combination of oxaliplatin and capecitabine (XELOX) as neoadjuvant chemotherapy regimens for the treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma. Methods A total of 300 patients aged 20-60 years with resectable gastric or gastroesophageal junction adenocarcinoma who were evaluated with cT3/4Nany were randomly assigned into 3 groups: DOX group (n = 100, treated with neoadjuvant DOX plus adjuvant XELOX), XELOX group (n = 100, treated with perioperative XELOX), and surgery group (n = 100, treated with adjuvant XELOX). Results A total of 93, 92, and 95 patients were enrolled in the DOX, XELOX, and surgery groups, respectively. The pathological complete response (pCR) rate was 16.1% in the DOX group and 4.3% in the XELOX group (P = 0.008). There were 56 (61.3%) patients in the DOX group who presented with surgical complications, 22 (23.9%) patients in the XELOX group, and 37 (38.9%) patients in the surgery group. The most common grade 3-4 adverse events in these three groups were neutropenia (32.3%, 30.4%, and 21.1%), leucopenia (21.5%, 22.8%, and 15.8%), nausea (15.1%, 16.3%, and 12.6%), and fatigue (10.8%, 7.6%, and 8.4%). Conclusions Neoadjuvant DOX is an effective and feasible regimen and might represent an option for young and middle-aged patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma.
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Lin JX, Xu YC, Lin W, Xue FQ, Ye JX, Zang WD, Cai LS, You J, Xu JH, Cai JC, Tang YH, Xie JW, Li P, Zheng CH, Huang CM. Effectiveness and Safety of Apatinib Plus Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer: A Nonrandomized Controlled Trial. JAMA Netw Open 2021; 4:e2116240. [PMID: 34241629 PMCID: PMC8271357 DOI: 10.1001/jamanetworkopen.2021.16240] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 05/03/2021] [Indexed: 02/03/2023] Open
Abstract
IMPORTANCE Apatinib is a novel treatment option for chemotherapy-refractory advanced gastric cancer (GC), but it has not been evaluated in patients with locally advanced GC. OBJECTIVE To investigate the effectiveness and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally advanced GC. DESIGN, SETTING, AND PARTICIPANTS This multicenter, prospective, single-group, open-label, phase 2 nonrandomized controlled trial was conducted in 10 centers in southern China. Patients with M0 and either clinical T2 to T4 or N+ disease were enrolled between July 1, 2017, and June 30, 2019. Statistical analysis was performed from December 1, 2019, to January 31, 2020. INTERVENTIONS Eligible patients received apatinib (500 mg orally once daily on days 1 to 21 and discontinued in the last cycle) plus SOX (S-1: 40-60 mg orally twice daily on days 1 to 14; oxaliplatin: 130 mg/m2 intravenously on day 1) every 3 weeks for 2 to 5 cycles. A D2 gastrectomy was performed 2 to 4 weeks after the last cycle. MAIN OUTCOMES AND MEASURES The primary end point was R0 resection rate. Secondary end points were the response rate, toxic effects, and surgical outcome. RESULTS A total of 48 patients (mean [SD] age, 63.2 [8.2] years; 37 men [77.1%]) were enrolled in this study. Forty patients underwent surgery (38 had gastrectomy, and 2 had exploratory laparotomy), with an R0 resection rate of 75.0% (95% CI, 60.4%-86.4%). The radiologic response rate was 75.0%, and T downstaging was observed in 16 of 44 patients (36.4%). The pathological response rate was 54.2% (95% CI, 39.2%-68.6%); moreover, this rate was significantly higher in patients who achieved a radiologic response compared with those who did not (12 [80.0%] vs 1 [20.0%]; P = .03) and in those who had an Eastern Cooperative Oncology Group Performance Status score of 0 (20 [76.9%] vs 10 [45.5%]; P = .03) or had tumors located in the upper one-third of the stomach (16 [61.5%] vs 7 [31.8%]; P = .04). Patients who achieved a pathological response (vs those who did not) had significantly less blood loss (median [range]: 60 [10-200] mL vs 80 [20-300] mL; P = .04) and significantly more lymph nodes harvested (median [range]: 40 [24-67] vs 32 [19-51]; P = .04) during surgery. Postoperative complications were observed in 7 of 38 patients (18.4%). Grade 3 toxic effects occurred in 16 of 48 patients (33.3%), and no grade 4 toxic effects or preoperative deaths were observed. CONCLUSIONS AND RELEVANCE This nonrandomized controlled trial found that apatinib combined with SOX was effective and had an acceptable safety profile as a neoadjuvant treatment for locally advanced GC. A large-scale randomized clinical trial may be needed to confirm the findings. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03192735.
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Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Yan-Chang Xu
- Department of Gastrointestinal Surgery, The First Hospital of Putian, Putian, Fujian Province, China
| | - Wei Lin
- Department of Gastrointestinal Surgery and Gastrointestinal Surgery Research Institute, The Affiliated Hospital of Putian University, Putian, Fujian Province, China
| | - Fang-Qin Xue
- Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, China
| | - Jian-Xin Ye
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
| | - Wei-Dong Zang
- Department of Gastrointestinal Surgery, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
| | - Li-Sheng Cai
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China
| | - Jun You
- Department of Gastrointestinal Oncology Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China
| | - Jian-Hua Xu
- Department of Oncology Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Jian-Chun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian Province, China
| | - Yi-Hui Tang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
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Zhao Q, Lian C, Huo Z, Li M, Liu Y, Fan L, Tan B, Zhao X, Zhang Z, Wang D, Liu Y, Guo H, Yang P, Tian Y, Li Y. The efficacy and safety of neoadjuvant chemotherapy on patients with advanced gastric cancer: A multicenter randomized clinical trial. Cancer Med 2020; 9:5731-5745. [PMID: 32583567 PMCID: PMC7433829 DOI: 10.1002/cam4.3224] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 05/04/2020] [Accepted: 05/15/2020] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVES Exploring the efficacy and safety of perioperative chemotherapy on patients with AGC at different clinical and pathological stages. METHODS A phase III randomized, multicenter, trial comparing adjuvant (arm A) or perioperative S-1 plus oxaliplatin (SOX, arm B), and perioperative capecitabine plus oxaliplatin (XELOX, arm C) was initiated in T3/4, node + gastric cancer patients (unclear). Each patient received an 8-cycle chemotherapy (3 weeks for one cycle). Group arms B and C received two cycles preoperatively, and six cycles postoperatively. Primary endpoints were R0 resection rate and DFS, and secondary endpoints included OS, ORR, DCR, and safety. This study was registered on Clinicaltrials.gov. NCT01516944. RESULTS A total of 749 patients were randomly assigned into groups A, B, and C. Group A received 1460 circles chemotherapy and group B received 1177 circles while group C received 1200 circles. R0 resection rates in the three groups were 81.7%, 88.7%, and 83.1%, respectively. The difference between groups A and B was considered to be statistically significant (P = .018), and no significant difference between groups B and C (P = .051). Hazard ratio were compared between groups B and C and DFS showed 0.72 (0.67-0.77 with 95% CI), Pnon-inferiority < .0001, Plog-rank = .064). The CI top limit actually lower than the estimated value of 1.38, which indicated noninferiority of SOX to XELOX. CONCLUSIONS Compared with PAC, perioperative chemotherapy showed a significant improvement in R0 resection rates and prognosis in AGC patients with higher safety rates. This study was powered to show superiority of perioperative over adjuvant SOX, and noninferiority of SOX to XELOX. Volume measurement, repeated laparoscopic exploration combined with exfoliative cytology can be used as a supplementary method in the clinical staging and efficacy evaluation of AGC.
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Affiliation(s)
- Qun Zhao
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Changhong Lian
- Surgical OncologyChangzhi Medical College Affiliated Peace HospitalChangzhiShanxiChina
| | - Zhibin Huo
- Gastrointestinal Tumor SurgeryXingtai People's HospitalXingtaiChina
| | - Ming Li
- General SurgeryThe First Hospital of ShijiazhuangShijiazhuangChina
| | - Yang Liu
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Liqiao Fan
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Bibo Tan
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Xuefeng Zhao
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Zhidong Zhang
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Dong Wang
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Yu Liu
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Honghai Guo
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Peigang Yang
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Yuan Tian
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Yong Li
- Department of General SurgeryThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
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van den Ende T, Abe Nijenhuis FA, van den Boorn HG, Ter Veer E, Hulshof MCCM, Gisbertz SS, van Oijen MGH, van Laarhoven HWM. COMplot, A Graphical Presentation of Complication Profiles and Adverse Effects for the Curative Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2019; 9:684. [PMID: 31403035 PMCID: PMC6677173 DOI: 10.3389/fonc.2019.00684] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 07/11/2019] [Indexed: 12/24/2022] Open
Abstract
Background: For the curative treatment of gastric cancer, several neoadjuvant, and adjuvant treatment-regimens are available which have shown to improve overall survival. No overview is available regarding toxicity and surgery related outcomes. Our aim was to construct a novel graphical method concerning adverse events (AEs) associated with multimodality treatment and perform a meta-analysis to compare different clinically relevant cytotoxic regimens with each other. Methods: The PubMed, EMBASE, CENTRAL, and ASCO/ESMO databases were searched up to May 2019 for randomized controlled trials investigating curative treatment regimens for gastric cancer. To construct single and bidirectional bar-charts (COMplots), grade 1–2 and grade 3–5 AEs were extracted per cytotoxic regimen. For surgery-related outcomes a pre-specified set of complications was used. Thereafter, treatment-arms comparing the same regimens were combined in a single-arm random-effects meta-analysis and pooled-proportions were calculated with 95% confidence-intervals. Comparative meta-analyses were performed based on clinical relevance and compound similarity. Results: In total 16 RCTs (n = 4,526 patients) were included investigating pre-operative-therapy and 39 RCTs investigating adjuvant-therapy (n = 13,732 patients). Pre-operative COMplots were created for among others; 5-fluorouracil/leucovorin-oxaliplatin-docetaxel (FLOT), epirubicin-cisplatin-fluoropyrimidine (ECF), cisplatin-fluoropyrimidine (CF), and oxaliplatin-fluoropyrimidine (FOx). Pre-operative FLOT showed a minor increase in grade 1–2 and grade 3–4 AEs compared to pre-operative ECF, CF, and FOx. A pooled analysis of patients who had received pre-operative therapy compared to patients who underwent direct surgery did not reveal any significant difference in surgery related morbidity/mortality. When we compared three commonly used adjuvant regimens; S-1 had the lowest amount of grade 3–4 AEs compared to capecitabine with oxaliplatin (CAPOX) and 5-FU with radiotherapy (5-FU+RT). Conclusion: COMplot provides a novel tool to visualize and compare treatment related AEs for gastric cancer. Based on our comparisons, pre-operative FLOT had a manageable toxicity profile compared to other pre-operative doublet or triplet regimens. We found no evidence indicating surgical outcomes might be hampered by pre-operative therapy. Adjuvant S-1 had a more favorable toxicity profile compared to CAPOX and 5-FU+RT.
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Affiliation(s)
- Tom van den Ende
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Frank A Abe Nijenhuis
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Héctor G van den Boorn
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Emil Ter Veer
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Maarten C C M Hulshof
- Department of Radiotherapy, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Suzanne S Gisbertz
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Martijn G H van Oijen
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Hanneke W M van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
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