Phase II Trial of Cisplatin, Interferon α-2b, Doxorubicin, and 5-Fluorouracil for Biliary Tract Cancer

The aim of this study was to test the efficacy of a chemotherapy combination of cisplatin, IFN α-2b, doxorubicin, Adriamycin, and 5-fluorouracil (PIAF) as treatment for radiologically measurable cancer of the biliary tree. Forty-one patients (19 gallbladder carcinoma and 22 cholangiocarcinoma) with unresectable, histologically confirmed adenocarcinoma were registered. Starting chemotherapy doses were as follows: cisplatin, 80 mg/m 2 i.v. over 2 h; doxorubicin, 40 mg/m 2 i.v. over 2 h; and 5-fluorouracil, 500 mg/m 2 by continuous infusion daily for 3 days. IFN α-2b (5 × 10 6 units/m 2 ) was administered s.c. before the cisplatin and daily thereafter for a total of four doses. The overall response rate was 21.1% [95% confidence interval (CI), 10–37]. For cholangiocarcinoma and gallbladder carcinoma patients, the response rates were 9.5% (95% CI, 1–32%) and 35.3% (95% CI, 14–62%), respectively. Overall median survival time was 14 months (95% CI, 9.5–18.5), 18.1 months (95% CI, 12.1–24.1) for the cholangiocarcinoma patients, and 11.5 months (95% CI, 5.9–17.1) for the gallbladder carcinoma patients. This difference was not statistically significant. The most common grade III and IV toxicities were neutropenia (41%), thrombocytopenia (20%), nausea and vomiting (34%), and fatigue (20%). In conclusion, the PIAF combination seemed more active against gallbladder carcinoma than against cholangiocarcinoma but was associated with significant toxicity. Therefore, this regimen cannot be recommended for cholangiocarcinoma, but it may have a role in the treatment of gallbladder carcinoma, particularly among patients who were refractory to higher priority investigational agents.