title: Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer.
abstract: 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.
authors.affiliation: Department of Gastrointestinal Medical Oncology and Digestive Diseases, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Patt
authors.forename: M M
authors.initials: MM
authors.lastname: Hassan
authors.forename: R D
authors.initials: RD
authors.lastname: Lozano
authors.forename: K A
authors.initials: KA
authors.lastname: Waugh
authors.forename: A M
authors.initials: AM
authors.lastname: Hoque
authors.forename: A I
authors.initials: AI
authors.lastname: Frome
authors.forename: S
authors.initials: S
authors.lastname: Lahoti
authors.forename: L
authors.initials: L
authors.lastname: Ellis
authors.forename: J N
authors.initials: JN
authors.lastname: Vauthey
authors.forename: S A
authors.initials: SA
authors.lastname: Curley
authors.forename: I I
authors.initials: II
authors.lastname: Schnirer
authors.forename: I
authors.initials: I
authors.lastname: Raijman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil