A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer

Abstract

Background: Optimal chemotherapy for advanced biliary tract cancer (BTC) is yet to be defined. We carried out this study to evaluate the efficacy and toxicity of combination chemotherapy with S-1 and cisplatin in metastatic or relapsed BTC. , and progressive disease in 9 (18%). With a median follow-up of 12.4 months, the median time to progression was 4.8 months (95% CI, 3.3-6.3) and median overall survival was 8.7 months (95% CI, 6.0-11.4). Major toxic effects were grade 3/4 neutropenia (8.9% of all cycles) and febrile neutropenia was observed in six cycles (2.7% of all cycles). Conclusion:Combination chemotherapy with S-1 and cisplatin was a moderately effective outpatient-based regimen in BTC patients. Toxic effects were moderate but manageable.

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

“…However, no standard chemotherapy regimen for advanced BTC has been established. Several phase II trials with new chemotherapeutic agents, such as gemcitabine (6)(7)(8)(9)(10), capecitabine (11), oxaliplatin (12), or S-1 (13,14) have demonstrated tumor response in ~15-35% of patients treated with single agents, and in 20-40% of patients treated with their combinations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Among them, gemcitabine has shown promising activity against advanced BTC, and has been commonly used for patients with unresectable or recurrent BTC in Japan.…”

Efficacy and Safety of S-1 Monotherapy in Patients with Advanced Biliary Tract Adenocarcinoma

“…A randomized trial showed that patients with advanced BTA who were treated with 5-FU-based palliative chemotherapy had better survival and a better quality of life than patients given the best supportive care alone [1]. Many cytotoxic agents, including 5-FU, cisplatin, gemcitabine, mitomycin C, oxaliplatin and docetaxel, have been tested against BTA, but none was significantly better when given alone or as part of a combination therapy [2,3,4,5,6,7,8,9,10]. …”

“…for 4 weeks in 6-week cycles) achieved a partial response, 47% had stable disease, and the median overall survival (OS) was 8.3 months. Based on these and other studies of S-1, several combination chemotherapies based on S-1 are currently being tested for the treatment of BTA [4]. …”

Outcome of Infusional 5-Fluorouracil, Doxorubicin, and Mitomycin-C (iFAM) Chemotherapy and Analysis of Prognostic Factors in Patients with Refractory Advanced Biliary Tract Cancer

“…A randomized phase III study demonstrated the superiority of GEM and cisplatin combination chemotherapy to single-agent GEM in patients with advanced BTC, which has made this combination chemotherapy an appropriate treatment option in patient with advanced BTC [15]. 5-FU-based chemotherapy, which gave rise to improvement in quality of life and survival, is another treatment option [7,8,9,10,11]. Also, a systematic review of 2,810 patients with advanced BTC demonstrated that a combination regimen was better than single-agent therapy, and a two-drug regimen of 5-FU or GEM plus platinum was better than other combinations [24].…”

“…Thereafter, palliative chemotherapy agents including 5-FU, gemcitabine (GEM), cisplatin/oxaliplatin, mitomycin-C (MMC), doxorubicin, docetaxel, and irinotecan have been tested with response rates (RRs) ranging from 10–40% [5,6]. The most classic agent, 5-FU, yields overall RRs (ORRs) of 10% as a single agent and 20–40% with combination chemotherapy [7,8,9,10,11]. Also, GEM-based chemotherapy has been introduced as treatment for patients with BTC and has been reported to yield ORRs of 10–35% [12,13,14].…”