cisplatin + fluorouracil + interferon alfa-2b

The combination of cisplatin, fluorouracil (5-FU), and interferon alfa-2b is a chemotherapy regimen that has been studied in various cancer types, particularly head and neck cancers and urothelial cancers. This combination has been investigated in multiple clinical trials to evaluate its efficacy and safety profile. ## Dosing Information The dosing regimens used in clinical trials varied somewhat: - In one study, the regimen consisted of cisplatin 80 mg/m² on day one, followed by 5-fluorouracil 750 mg/m² as a daily infusion for 5 days and interferon alfa-2b 5 MU/m² subcutaneously[1]. - Another study used cisplatin at 100 mg/m², followed by 5-fluorouracil at 1,000 mg/m² by continuous infusion for 5 days, with interferon alfa-2b administered at varying doses[2]. - A phase III trial used cisplatin 100 mg/m² on day 1 and 5-FU 1,000 mg/m²/day by continuous infusion for 96 hours (days 1 to 4), with interferon alfa-2b 3 × 10⁶ U/day subcutaneously on days 1 to 5[3]. - In a study for urothelial cancer, the FAP regimen (fluorouracil, interferon alfa-2b, and cisplatin) was compared with doxorubicin[4]. ## Clinical Efficacy The combination has shown varying degrees of efficacy: - In head and neck cancer, a phase III trial found that adding interferon alfa-2b to cisplatin and 5-FU did not improve response rates or median survival compared to cisplatin and 5-FU alone[3]. - For urothelial cancer, the FAP combination showed promise in phase II studies with response rates of 65% and complete response rates of 18%[8]. - However, a subsequent phase III trial comparing FAP with M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in urothelial cancer found that while FAP had a higher response rate, the differences were not statistically significant, and FAP was associated with increased toxicity[6]. ## Toxicity Profile The combination therapy is associated with significant toxicities: - Common adverse effects include mucositis, myelosuppression, anorexia, fever, leukopenia, and thrombocytopenia[3][5]. - In comparative studies, FAP was associated with more mucocutaneous toxicity compared to other regimens like M-VAC, which had more myelosuppression[6]. - Dose-limiting toxicities included mucositis and myelosuppression, which required dose adjustments in clinical trials[5]. - Pharmacodynamic analyses showed that older age, female sex, and higher 5-FU area under the curve were associated with lower nadir counts and/or increased mucositis[5]. - Patients with diabetes mellitus experienced significantly increased myelosuppression, elevated serum creatinine, hypocalcemia, higher 5-FU concentrations, and lower 5-FU clearance compared to non-diabetics[5]. Despite showing activity in certain cancer types, the combination of cisplatin, fluorouracil, and interferon alfa-2b has not demonstrated clear superiority over standard chemotherapy regimens in phase III trials, and its use is limited by significant toxicity.

Other names

FAP regimencisplatin + 5-FU + interferon alfa-2b