Phase II study of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer

• Published in: Cancer chemotherapy and pharmacology Vol. 75; no. 4; pp. 711 - 718
• Main Authors: Kim, Hyeong Su, Kim, Ho Young, Zang, Dae Young, Oh, Ho Suk, Jeon, Jang Yong, Cho, Ji Woong, Park, Choong Kee, Kim, Jong Hyeok, Kim, Min-Jeong, Ha, Hong Il, Kim, Jung Han, Han, Boram, Song, Hunho, Kwon, Jung Hye, Choi, Dae Ro, Jung, Joo Young
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2015; Springer Nature B.V
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biliary Tract Neoplasms - drug therapy; Biliary Tract Neoplasms - pathology; Cancer Research; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Medicine; Medicine & Public Health; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Oncology; Original Article; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; Oxonic Acid - therapeutic use; Pharmacology/Toxicology; Tegafur - administration & dosage; Tegafur - adverse effects; Tegafur - therapeutic use; Phase II study; Gemcitabine; Biliary tract cancer; Combination chemotherapy; S-1
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-015-2687-x

Purpose A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC). Methods Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m 2 intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m 2 oral S-1 on days 1–14 of each cycle. The treatment was repeated every 3 weeks. Results Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6 %), intrahepatic and extrahepatic bile ducts in 23 (60.5 %), and the ampulla of Vater in 3 (7.9 %) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6 % (95 % CI 8.5–36.7] in the per-protocol (PP) population, and 18.4 % (95 %CI 6.1–30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5 % (95 %CI 60.6–87.6) in the PP population. The median progression-free survival was 4.4 months (95 %CI 1.8–6.9), and the median overall survival was 9.0 months (95 %CI 4.0–13.9) with a 1-year survival rate of 44.7 % (95 %CI 29.0–61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1 %), 9 (25.7 %), 2 (5.7 %), and 2 (5.7 %) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4 %), anorexia (2.9 %), and renal toxicity (2.9 %). Conclusion Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.