5-fluorouracil plus folinic acid with or without ifosfamide in advanced colorectal cancer: a phase II randomized trial.

AIM: This phase II trial evaluated the biomodulation of 5-fluorouracil (5-FU) plus folinic acid (FA) with or without ifosfamide (IFO) in chemotherapy-naive patients with colorectal cancer. PATIENTS AND METHODS: Forty-eight patients were randomized to receive: FA (25 mg/m2 iv bolus days 1 to 3), followed by 5-FU (750 mg/m2 iv bolus days 1 to 3), arm A; or FA (25 mg/m2 iv bolus days 1 to 3), followed by 5-FU (750 mg/m2 iv bolus days 1 to 3) plus IFO (2,000 mg/m2 in 1000 mL 5% dextrose in a 2-hr infusion, days 1 to 3), arm B. Mesna was added during and after IFO to prevent hemorrhagic cystitis. Treatment was repeated every 21 days in both arms. RESULTS: Forty-five patients were assessable for response: in arm A, 5 patients achieved a partial response (overall response, 25%), and in arm B, 2 patients achieved a complete and 1 a partial response (overall response, 12%). Time to failure was 3.5 months (range, 1-38) in patients treated with 5-FU plus FA, and 3 months (range, 1-21) in patients treated with the IFO combination. The median survival time was 13.5 months (range, 1-49 months) in arm A and 16 months (range, 1-43 months) in arm B. Diarrhea, stomatitis and vomiting were the most common nonhematologic toxicities in both arms. The most notable hematologic toxicity was leukopenia; 15% and 20% of patients experienced grade 4 in arm A and arm B, respectively. CONCLUSIONS: IFO does not increase the activity of the 5-FU plus FA combination in advanced colorectal cancer.