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

Abstract

Objective: The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) as salvage chemotherapy in biliary tract cancer (BTC) and to identify prognostic factors. Methods: Fifty patients received 5-FU 800 mg/m² over 10 h on days 1–5, doxorubicin 30 mg/m² on day 1 and mitomycin-C 8 mg/m² on day 1, every 4 weeks. The primary endpoint was the overall survival (OS) rate at 6 months. Results: The responses to iFAM were as follows: partial response in 2 patients (4.2%) and stable disease in 9 patients (18.7%). The median progression-free survival and OS were 2.2 months and 5.6 months, respectively. The 6-month OS rate was 48%. Grade 3/4 adverse events included neutropenia (10%), thrombocytopenia (8%), and anemia (2%). Based on multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status, serum albumin, and response to previous chemotherapy were significantly associated with OS. Three risk groups based on the number of 3 poor prognostic factors (0 vs. 1 vs. 2–3) were well correlated to OS (8.7 vs. 5.5 vs. 2.4 months, respectively; p = 0.0002). Conclusions: iFAM as salvage regimen has modest effect and tolerable toxicity in advanced BTC. The described risk group classification may help guide treatment plans.

Second‐line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine‐platinum combination: A large multicenter study by the Association des Gastro‐Entérologues Oncologues

“…Fluoropyrimidines (especially S‐1) were some of the main CT2s tested, with very varied survival rates reported for gemcitabine‐refractory Asian patients . In addition to single agents, combinations of conventional chemotherapeutic drugs and targeted therapies have been assessed with conflicting or disappointing results . Among them, sunitinib recently showed promising results in 53 patients with intrahepatic cholangiocarcinomas with median PFS and OS times of 5.2 and 9.6 months, respectively, a DCR of 86%, and good tolerance .…”

Two-Week Combination Chemotherapy with Gemcitabine, High-Dose Folinic Acid and 5 Fluorouracil (GEMFUFOL) as First-Line Treatment of Metastatic Biliary Tract Cancers

“…The response rates to 5-fluorouracil, when used as single agent bolus or in prior combination studies, range from 0-34% (Falkson et al, 1984;Harvey et al, 1984;Kajanti et al, 1994;Gebbia et al, 1996;Croitoru et al, 2012). On the other hand, infusional schemes of 5-fluorouracil were shown to have higher response rates in biliary tract cancers (Chen et al, 1998;Lim et al, 2012). Additionally, it has been reported that the infusional schemes of 5-fluorouracil had a more advantageous side effect profile, and they were better tolerated than bolus administration.…”

A Retrospective Study of Gemcitabine and Cisplatin Combination Therapy as Second-Line Treatment for Advanced Biliary Tract Cancer

“…Only limited studies have previously been reported (table 4) [13,14,15,16,17,18,19,20,21,22,23,24]. In a large retrospective study that included several regimens of second-line treatment, objective response rates and disease control rates were reported to be 9 and 43%, respectively [25].…”