Phase II trial of cisplatin, interferon alpha-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 alpha-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 alpha-2b (5 x 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.

Pilot study of concurrent 5-fluorouracil/paclitaxel plus radiotherapy in patients with carcinoma of the esophagus and gastroesophageal junction.

Preoperative concurrent chemotherapy and radiotherapy can be highly effective but are often associated with significant rates of morbidity and even mortality. We studied the toxicity of continuous infusion of 5-fluorouracil (5-FU) and weekly paclitaxel combined with radiotherapy. Patients had histologic proof of local-regional carcinoma of the esophagus or gastroesophageal (GE) junction, a Karnofsky performance status of 70 or greater, and normal liver, renal, and bone marrow functions. Chemotherapy consisted of continuous infusion of 5-FU (300 mg/m2/d) for 5 days a week for 5 weeks, plus paclitaxel (45 mg/m2) given during 3 hours every week for 5 weeks. Based on the tumor location and its resectability, the total dose of concurrent radiation varied between 45 Gy and 50.4 Gy. Nine men and one woman, with a median age of 61 years, were evaluated. One had GE junction cancer, six had distal esophageal cancer, and three had midesophageal cancer. Weight loss, nausea, vomiting, and dysphagia of grades I and II were noted. The hematologic toxicity was mild. No patients required transfusion. There was no leukopenia or thrombocytopenia. None of the patients was hospitalized during chemoradiation; all patients completed treatment as outpatients. Five patients had subsequent surgical resections: one had a pathologically complete response, and two had a partial response (>90% necrosis). Continuous infusion of 5-FU plus paclitaxel given concurrently with radiotherapy was well tolerated. We plan to study this regimen further in upper gastrointestinal cancers.