Cisplatin-Based Combination Chemotherapy for Advanced Hepatocellular Carcinoma: A Single Center Experience before the Sorafenib Era
3
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose Systemic chemotherapy is the only option for patients with unresectable/metastatic hepatocellular carcinoma (HCC) who are not candidates for local/regional treatment. However, the response to such treatment and survival are poor, especially in hepatitis B virus (HBV) endemic areas. The aim of this study was to determine the efficacy of cisplatin-based combination chemotherapy and identify a subgroup of advanced HCC patients with favorable responses. Materials and Methods The medical records of all consecutive patients with unresectable/metastatic HCC who received cisplatin-based combination chemotherapy between January 2003 and October 2009 were reviewed. Time to progression (TTP) and overall survival (OS) were determined using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify prognostic factors for TTP and OS. Results Data for 46 patients were analyzed. First-line chemotherapies consisted of cisplatin-based combination treatment with doxorubicin, fluoropyrimidines and gemcitabine. The response rate for all patients was 4.3%. The median TTP and OS were 1.8 (95%confidence interval [CI], 1.1 to 2.5) and 7.2 (95% CI, 3.0 to 11.5) months, respectively. Eastern Cooperative Oncology Group (ECOG) performance status (PS), Child classification, Cancer of the Liver Italian Program (CLIP) score and portal vein thrombosis (PVT) were identified by univariate analyses as prognostic factors for TTP and OS. ECOG PS (hazard ratio [HR], 4.51; 95%CI, 1.61 to 12.6; p=0.004) and PVT (HR, 2.12; 95%CI, 1.10 to 4.11; p=0.026) were independent prognostic factors for TTP. Conclusion Cisplatin-based combination chemotherapy in patients with advanced HCC has a low response rate and short TTP regardless of the chemotherapy regimen used. Patients with a good ECOG PS and without PVT can be considered candidates for cisplatin-based combination chemotherapy.
Abstract
Purpose Systemic chemotherapy is the only option for patients with unresectable/metastatic hepatocellular carcinoma (HCC) who are not candidates for local/regional treatment. However, the response to such treatment and survival are poor, especially in hepatitis B virus (HBV) endemic areas. The aim of this study was to determine the efficacy of cisplatin-based combination chemotherapy and identify a subgroup of advanced HCC patients with favorable responses. Materials and Methods The medical records of all consecutive patients with unresectable/metastatic HCC who received cisplatin-based combination chemotherapy between January 2003 and October 2009 were reviewed. Time to progression (TTP) and overall survival (OS) were determined using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify prognostic factors for TTP and OS. Results Data for 46 patients were analyzed. First-line chemotherapies consisted of cisplatin-based combination treatment with doxorubicin, fluoropyrimidines and gemcitabine. The response rate for all patients was 4.3%. The median TTP and OS were 1.8 (95%confidence interval [CI], 1.1 to 2.5) and 7.2 (95% CI, 3.0 to 11.5) months, respectively. Eastern Cooperative Oncology Group (ECOG) performance status (PS), Child classification, Cancer of the Liver Italian Program (CLIP) score and portal vein thrombosis (PVT) were identified by univariate analyses as prognostic factors for TTP and OS. ECOG PS (hazard ratio [HR], 4.51; 95%CI, 1.61 to 12.6; p=0.004) and PVT (HR, 2.12; 95%CI, 1.10 to 4.11; p=0.026) were independent prognostic factors for TTP. Conclusion Cisplatin-based combination chemotherapy in patients with advanced HCC has a low response rate and short TTP regardless of the chemotherapy regimen used. Patients with a good ECOG PS and without PVT can be considered candidates for cisplatin-based combination chemotherapy.
참고문헌 (25)
- Nowak AK, "Systemic therapy for advanced hepatocellular carcinoma: a review", Eur J Cancer, 40, pp.1474~1484 (2004)
- Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)
- Cheng AL, "Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial", Lancet Oncol, 10, pp.25~34 (2009)
- Sciarrino E, "Adriamycin treatment for hepatocellular carcinoma: experience with 109 patients", Cancer, 56, pp.2751~2755 (1985)
- Okada S, "A phase 2 study of cisplatin in patients with hepatocellular carcinoma", Oncology, 50, pp.22~26 (1993)
- Lee J, "Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma", Cancer Chemother Pharmacol, 54, pp.385~390 (2004)
- Parikh PM, "A phase II study of gemcitabine and cisplatin in patients with advanced hepatocellular carcinoma", Trop Gastroenterol, 26, pp.115~118 (2005)
- Lee JO, "Combination chemotherapy with capecitabine and cisplatin for patients with metastatic hepatocellular carcinoma", Ann Oncol, 20, pp.1402~1407 (2009)
- Ikeda M, "A phase II trial of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin for metastatic hepatocellular carcinoma", Cancer, 103, pp.756~762 (2005)
- Lai CL, "Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma: a prospective randomized trial", Cancer, 62, pp.479~483 (1988)
- Yeo W, "A randomized phase III study of doxorubicin versus cisplatin", interferon alpha-2b, fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma, pp.J Natl Cancer Inst, 2005[DOI]
- 강보리, "간세포암 환자에서 doxorubicin과 cisplatin 복합 화학 요법에 대한 제 2상 임상연구", 대한내과학회지, 68(2), pp.203~210 (2005), 대한내과학회
- Kong XB, "Overexpression of P-glycoprotein in hepatocellular carcinoma and its clinical implication", World J Gastroenterol, 6, pp.1234~135 (2000)
- Katiyar S, "P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India", Cancer, 88, pp.1565~1573 (2000)
- Park JW, "Practice guideline for diagnosis and treatment of hepatocellular carcinoma", 가정의학회지, 10, pp.88~98 (2004)
- American Joint Committee on Cancer, "AJCC Cancer Staging Manual. 6th ed" (2002), Springer
- "A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators", Hepatology, 28, pp.751~755 (1998)
- Therasse P, "New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada", J Natl Cancer Inst, 92, pp.205~216 (2000)
- The Cancer of the Liver Italian Program (CLIP) Investigators, "Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma", Hepatology, 31, pp.840~845 (2000)
- Farinati F, "How should patients with hepatocellular carcinoma be staged? Validation of a new prognostic system", Cancer, 89, pp.2266~2273 (2000)
- Levy I, "Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto", Gut, 50, pp.881~885 (2002)
- Ueno S, "Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program", Hepatology, 34, pp.529~534 (2001)
- Leung TW, "Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxorubicin and 5-fluorouracil chemotherapy", Cancer, 94, pp.421~427 (2002)
- Zhang XB, "Hepatocellular carcinoma with main portal vein tumor thrombus: treatment with 3-dimensional conformal radiotherapy after portal vein stenting and transarterial chemoembolization", Cancer, 115, pp.1245~1252 (2009)
- Tan CK, "Simple clinical prognostic model for hepatocellular carcinoma in developing countries and its validation", J Clin Oncol, 21, pp.2294~2298 (2003)