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Ding Y, Wang S, Qiu Z, Zhu C, Wang Y, Zhao S, Qiu W, Wang K, Lv J, Qi W. The worthy role of hepatic arterial infusion chemotherapy in combination with anti-programmed cell death protein 1 monoclonal antibody immunotherapy in advanced hepatocellular carcinoma. Front Immunol 2023; 14:1284937. [PMID: 38022559 PMCID: PMC10644007 DOI: 10.3389/fimmu.2023.1284937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 10/19/2023] [Indexed: 12/01/2023] Open
Abstract
Systemic therapy remains the primary therapeutic approach for advanced hepatocellular carcinoma (HCC). Nonetheless, its efficacy in achieving control of intrahepatic lesions is constrained. Hepatic arterial infusion chemotherapy (HAIC) is a therapeutic approach that combines localized treatment with systemic antitumor effects, which aim is to effectively manage the progression of cancerous lesions within the liver, particularly in patients with portal vein tumor thrombosis (PVTT). Combining HAIC with anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody (mAb) immunotherapy is anticipated to emerge as a novel therapeutic approach aimed at augmenting the response inside the localized tumor site and achieving prolonged survival advantages. In order to assess the effectiveness, safety, and applicability of various therapeutic modalities and to address potential molecular mechanisms underlying the efficacy of HAIC-sensitizing immunotherapy, we reviewed the literature about the combination of HAIC with anti-PD-1 mAb therapies.
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Affiliation(s)
- Yixin Ding
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Shasha Wang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Zhenkang Qiu
- Interventional Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chunyang Zhu
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Yan Wang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Shufen Zhao
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Wensheng Qiu
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Kongjia Wang
- Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jing Lv
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Weiwei Qi
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
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Xu Y, Fu S, Mao Y, Huang S, Li D, Wu J. Efficacy and safety of hepatic arterial infusion chemotherapy combined with programmed cell death protein-1 antibody and lenvatinib for advanced hepatocellular carcinoma. Front Med (Lausanne) 2022; 9:919069. [PMID: 36117969 PMCID: PMC9474651 DOI: 10.3389/fmed.2022.919069] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 07/07/2022] [Indexed: 11/13/2022] Open
Abstract
Background The purpose of the study was to assess the efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) who are undergoing hepatic arterial infusion chemotherapy (HAIC) combined with programmed cell death protein-1 (PD-1) antibody and lenvatinib. Methods We retrospectively evaluated 61 patients treated with HAIC combined with PD-1 antibody and lenvatinib at the Second Affiliated Hospital of Nanchang University between September 2020 and January 2022 for advanced HCC. We analyzed tumor response, progression free survival (PFS), and treatment-related adverse events (TRAEs). Results The objective response rate (ORR) was 36.1% (RECIST 1.1)/57.4% (mRECIST) and the disease control rate (DCR) was 82.0%. The overall median PFS was 6.0 months, 6.7 months for first-line treatment, and 4.3 months for second-line treatment. The most common TRAEs were neutropenia (50.8%), abdominal pain (45.9%), and aspartate aminotransferase increase (39.3%). Conclusion Hepatic arterial infusion chemotherapy combined with PD-1 antibody and lenvatinib is effective in the treatment of advanced HCC, and the TRAEs are generally controllable.
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Affiliation(s)
| | | | | | | | | | - Jianbing Wu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Motegi S, Yokoo T, Nozawa R, Azumi R, Kawata Y, Ogawa K, Setsu T, Mizuno KI, Nishino K, Umezu H, Kawai H, Suda T, Terai S. Long-term survival of 11 years with multidisciplinary therapy for hepatocellular carcinoma metastasis to the ovary and peritoneum: a case report. Clin J Gastroenterol 2021; 14:1211-1220. [PMID: 33978943 PMCID: PMC8298212 DOI: 10.1007/s12328-021-01434-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/02/2021] [Indexed: 02/07/2023]
Abstract
We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.
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Affiliation(s)
- Satoko Motegi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
- Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life, School of Medicine, Niigata University, Niigata, Niigata, Japan.
| | - Ryosuke Nozawa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Rie Azumi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Yuzo Kawata
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Kohei Ogawa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Ken-Ichi Mizuno
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Koji Nishino
- Department of Obstetrics and Gynecology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Hajime Umezu
- Division of Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Hirokazu Kawai
- Department of Internal Medicine, Niigata Prefectural Shibata Hospital, Shibata, Niigata, Japan
| | - Takeshi Suda
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine Niigata University Hospital, Minamiuonuma, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
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Yamamoto S, Onishi H, Takaki A, Oyama A, Adachi T, Wada N, Sakata M, Yasunaka T, Shiraha H, Okada H. The Early Decline of α-Fetoprotein and Des-γ-Carboxy Prothrombin Predicts the Response of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients. Gastrointest Tumors 2020; 7:83-92. [PMID: 32903927 DOI: 10.1159/000506941] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 03/01/2020] [Indexed: 01/22/2023] Open
Abstract
Introduction Molecular targeting drugs are recommended as second-line treatment for intrahepatic advanced hepatocellular carcinoma (HCC). However, in Asia, hepatic arterial infusion chemotherapy (HAIC) is also considered as a second-line treatment because it improves the survival of responders. The aim of this study was to predict responders and non-responders to HAIC with low-dose cisplatin plus 5-fluorouracil (LFP) using tumor markers. Objective and Methods The data of 47 patients who received LFP for the first time in our hospital were analyzed retrospectively. We evaluated the association between treatment response by Response Evaluation Criteria in Solid Tumors and the changing ratio of the serum concentration of α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxy prothrombin (DCP) 2 weeks after LFP initiation. Results The number of patients showing a complete response (CR), a partial response (PR), stable disease (SD), and progressive disease (PD) was 0 (0%), 20 (43%), 18 (38%), and 9 (19%), respectively. The AFP ratio showed significant positive correlations for PR vs. SD (p = 0.004) and PR vs. PD (p = 0.003). The DCP ratio correlated significantly for PR vs. SD (p = 0.02). The optimal cutoff values for responders were 0.79 for the AFP ratio and 0.53 for the DCP ratio. Prediction using both or either cutoff value showed 93% sensitivity, 53% specificity, a 94% negative predictive value, and a 57% positive predictive value. Conclusion Optimal cutoff values for AFP and DCP ratios enable prediction of nonresponders to HAIC with LFP. This simple and early assessment method allows the use of HAIC and molecular targeting drugs for HCC treatment.
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Affiliation(s)
- Shumpei Yamamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hideki Onishi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Akinobu Takaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Atsushi Oyama
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Takuya Adachi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Nozomu Wada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Masahiro Sakata
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Tetsuya Yasunaka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hidenori Shiraha
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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Si T, Chen Y, Ma D, Gong X, Guan R, Shen B, Peng C. Transarterial chemoembolization prior to liver transplantation for patients with hepatocellular carcinoma: A meta-analysis. J Gastroenterol Hepatol 2017; 32:1286-1294. [PMID: 28085213 DOI: 10.1111/jgh.13727] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 12/28/2016] [Accepted: 01/08/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM A debate exists over whether using preoperative transarterial chemoembolization for patients with hepatocellular carcinoma before liver transplantation. Numerous studies have been investigating on this, but there is still no unanimous conclusion about the effect of preoperative transarterial chemoembolization. We conducted the meta-analysis of all available studies to systematically evaluate the influence of preoperative transarterial chemoembolization on liver transplant. METHODS A systematic search was performed by two authors (Si TF. and Guan RY.) through PubMed, Embase, Cochrane, and Science Citation Index Expanded, combined with Manual Retrieval and Cited Reference Search. The searching cut-off date was 2016/07/31, and all the data obtained were statistically analyzed using Review Manager version 5.1 software (Copenhagen, The Nordic Cochrane Center, The Cochrane Collaboration, 2011) recommended by Cochrane Collaboration. RESULTS The study showed that there was no difference between the experimental group and the control group on perioperative mortality (RR = 1.10, 95% confidence interval (CI) = [0.49-2.48], P = 0.82) or biliary complications (RR = 0.96, 95%CI = [0.66-1.39], P = 0.83). Preoperative transarterial chemoembolization had no obvious effect on improving overall survival (HR = 1.05, 95%CI = [0.65-1.72], P = 0. 83) but would result in a higher rate of vascular complications (RR = 2.01, 95%CI = [1.23-3.27], P = 0.005) and a reduction of disease free survival (HR = 1.66, 95%CI = [1.02-2.70], P = 0.04). Subgroup analysis also revealed that patients from transarterial chemoembolization group in Asia had a much lower overall survival rate (HR = 2.65, 95%CI = [1.49-4.71], P = 0.0009) compared with the control group. CONCLUSIONS Considering the possible adverse impacts on liver transplantation and the variation in sensitivity to transarterial chemoembolization, clinicians should be more cautious when considering transarterial chemoembolization as the bridging therapy for patients in the waiting list.
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Affiliation(s)
- Tengfei Si
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yongjun Chen
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Di Ma
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiaoyong Gong
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ruoyu Guan
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Boyong Shen
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chenghong Peng
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Momiyama K, Nagai H, Ogino Y, Mukouzu T, Matsui D, Kogame M, Matsui T, Wakui N, Shinohara M, Igarashi Y, Sumino Y. The Importance of Lamivudine Therapy in Liver Cirrhosis Patients Related HBV with Advanced Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy. ACTA ACUST UNITED AC 2015; 2:112-118. [PMID: 27595062 PMCID: PMC4997933 DOI: 10.2174/2212697x02666150602220735] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Revised: 04/08/2015] [Accepted: 06/02/2015] [Indexed: 01/11/2023]
Abstract
Purpose: We have previously reported that continuous hepatic arterial infusion chemotherapy (HAIC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with liver cirrhosis (LC) related to HCV infection (C-LC) or alcohol abuse (A-LC) than in patients who had LC related to HBV infection (B-LC). The aim of the present study was to retrospectively assess the efficacy of lamivudine therapy for B-LC patients with aHCC undergoing HAIC. Methods: Seventeen adult Japanese B-LC patients with aHCC were treated by HAIC with or without lamivudine (100 mg/day) between 2002 and 2008 at our hospital. Their tumors were inoperable according to computed tomography findings. HAIC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was given via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. Results: Nine of the 17 patients received lamivudine at a dose of 100 mg/day together with HAIC (LAM group), while 8 patients did not receive lamivudine and only had HAIC (non-LAM group). The response rate was 12.5 in the non-LAM group and 0.0% in the LAM group. However, the survival of the LAM group was better than that of the non-LAM group, although there was no significant difference between them. The median survival time of the LAM and non-LAM groups was 310 and 157 days, respectively. HBV-DNA levels were significantly lower after chemotherapy compared with that before chemotherapy in the LAM group. In the non-LAM group, the percentage of Th2 cells before HAIC and after HAIC was significantly higher than in the control group. However, the percentage of Th2 cells in the LAM group after HAIC was not different from that in the control group, although it was significantly higher in the LAM group than in the control group before chemotherapy. Conclusions: These results indicate that lamivudine therapy may prolong the survival of B-LC patients receiving HAIC for aHCC by reducing HBV-DNA level and inhibiting the increase of Th2 cells in host immunity.
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Affiliation(s)
- Koichi Momiyama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Hidenari Nagai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Yu Ogino
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Takanori Mukouzu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Daigo Matsui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Michio Kogame
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Teppei Matsui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Noritaka Wakui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Mie Shinohara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Yoshinori Igarashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Yasukiyo Sumino
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
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Miyahara K, Nouso K, Yamamoto K. Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age. World J Gastroenterol 2014; 20:4151-9. [PMID: 24764653 PMCID: PMC3989951 DOI: 10.3748/wjg.v20.i15.4151] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 01/02/2014] [Accepted: 02/26/2014] [Indexed: 02/06/2023] Open
Abstract
The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma (HCC). After development of sorafenib and its introduction as a therapeutic agent used in the clinic, several critical questions have been raised. Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated. Although it is difficult to know the responders in advance using conventional characteristics of patients, there are specific serum cytokines and/or gene amplification in tumor tissues that have been reported to predict efficacy of sorafenib. Risk and benefits of continuation of sorafenib beyond radiological progression is another issue to consider because no other standard therapy for advanced HCC as yet exists. In addition, effectiveness of the expanded application of sorafenib is still controversial, although a few studies have shed some light on combinational treatment with sorafenib for intermediate-stage HCC. Recently, over 50 relevant drugs have been developed and are currently under investigation. The efficacy of some of these drugs has been extensively examined, but none have demonstrated any superiority over sorafenib, so far. However, there are several drugs that have shown efficacy for treatment after sorafenib failure, and these are proceeding to further studies. To address these issues and questions, we have done extensive literature review and summarize the most current status of therapeutic application of sorafenib.
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Multimodal therapy for liver cirrhosis patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 2010; 68:139-45. [PMID: 20857114 DOI: 10.1007/s00280-010-1465-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2010] [Accepted: 09/08/2010] [Indexed: 10/19/2022]
Abstract
PURPOSE We have previously shown that continuous intra-arterial combination chemotherapy (IACC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with HCV-related liver cirrhosis (C-LC) or alcoholic liver cirrhosis (A-LC) than in patients with HBV-related LC (B-LC). However, it is still unknown whether IACC actually improves the prognosis of aHCC patients with liver cirrhosis (LC), because it is difficult to perform a randomized controlled trial for patients with a poor prognosis. The aim of this study was to retrospectively assess the influence of IACC on the prognosis of aHCC. METHODS Fifty-eight adult Japanese patients who had aHCC and LC underwent repeated trans-arterial chemoembolization (TACE) without IACC between 1990 and 1997 at our hospital (group T), while 43 patients with aHCC and LC received IACC between 2000 and 2008 after undergoing several TACE sessions (group R). The Japan Integrated Staging score (JIS score) of each patient was ≥ 3 at the time of presentation, except for patients with tumor thrombi involving the first or subsequent portal vein branches or those with tumor invasion of the inferior vena cava. The same IACC regimen was repeated for as long as possible in group R. RESULTS In group T, 13 patients had B-LC, 37 patients had C-LC, and 8 patients had A-LC, while the respective numbers were 14, 21, and 8 in group R. The median survival time (MST) was 248 days for patients with C-LC in group T and 708 days for those in group R, while it was 253 days for patients with A-LC in group T and 593 days for those in group R. There were significant differences of survival between the two groups. However, MST was 369 days for patients with B-LC in group T and 782 days for those in group R, without a significant difference. In group R, a complete or partial response was achieved after 4 weeks of chemotherapy in 14.3% of patients with B-LC versus 42.9% of patients with C-LC and 37.5% of patients with A-LC. CONCLUSIONS In LC patients with a JIS score > 3 at diagnosis, multimodal therapy with IACC after TACE prolongs the MST of C-LC or A-LC patients compared with TACE alone, although it does not improve the MST of patients with B-LC.
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Woo HY, Bae SH, Park JY, Han KH, Chun HJ, Choi BG, Im HU, Choi JY, Yoon SK, Cheong JY, Cho SW, Jang BK, Hwang JS, Kim SG, Kim YS, Seo YS, Yim HJ, Um SH. A randomized comparative study of high-dose and low-dose hepatic arterial infusion chemotherapy for intractable, advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 2009; 65:373-82. [PMID: 19763572 DOI: 10.1007/s00280-009-1126-2] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2009] [Accepted: 09/02/2009] [Indexed: 12/17/2022]
Abstract
PURPOSE Hepatic arterial infusion chemotherapy (HAIC) has been reported to be effective in patients with advanced hepatocellular carcinoma (HCC). METHODS In this multicenter, prospective, open-labeled, clinical trial, we randomly assigned 68 patients with advanced HCC to receive either low-dose [n = 32, 5-fluorouracil (FU), 170 mg/m(2) and cisplatin, 7 mg/m(2) on days 1-5] or high-dose HAIC (n = 36, 5-FU, 500 mg/m(2) on days 1-3 and cisplatin, 60 mg/m(2) on day 2) every 4 weeks via an implantable port system. RESULTS A total of 207 cycles of HAIC was given to the 68 patients. Overall, 6 patients (8.8%) achieved a partial response and 21 patients (30.9%) had stable disease. The objective response rate (CR + PR) was significantly improved in the high-dose group compared to the low-dose group (16.7% vs. 0%, P = 0.024). The median time to disease progression and overall survival were slightly prolonged in the high-dose group compared to the low-dose group (median survival, 193 vs. 153 days; P = 0.108; median time to disease progression, 145 vs. 90 days; P = 0.095). Multivariate analysis showed that tumor response to treatment [P = 0.007, RR 2.27 (95% CI, 1.248-4.132)] was the only factor associated with overall survival. All adverse events were tolerable and successfully managed in both treatment groups. CONCLUSIONS Both HAIC regimens are safe and effective in patients with advanced HCC. High-dose HAIC achieves a better tumor response compared to low-dose HAIC.
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Affiliation(s)
- Hyun Young Woo
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
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