DOUBLE 5-FLUOROURACIL MODULATION WITH FOLINIC ACID AND RECOMBINANT INTERFERON-ALPHA-2B - A PHASE-I-II STUDY IN METASTATIC COLORECTAL-CANCERPATIENTS

Twenty-two patients with metastatic colorectal cancer entered a Phase I-II trial to assess the maximum tolerable dose of alpha-2B-interferon administered intramuscularly three times per week in combination with fixed doses of 5-fluorouracil (450 mg/m2 IV for 5 days, and, from day 28, weekly) and folinic acid (200 mg/m2 IV before 5-fluorouracil) and the efficacy of this combination. Diarrhea and mucositis were the mos t frequent 5-fluorouracil-related toxicities and were greater-than-or- equal-to ECOG grade 3 in 23% and 18% of patients, respectively. Of 15 patients receiving interferon greater-than-or-equal-to 9 X 10(6) IU, 1 0 required interferon dose reduction mostly because of severe fatigue, anorexia, and declining performance status. Among 19 patients evaluab le for response, 3 achieved a partial response and 1 a complete respon se for an overall response rate of 21% (95% confidence interval, 6-46% ). In conclusion, our study demonstrates that IFN-alpha2B at doses hig her than 6 X 10(6) IU intramuscularly three times per week in the comb ination with 5-fluorouracil and folinic acid we used is too toxic for the majority of patients; this combination has moderate activity in me tastatic colorectal cancer, although similar response rates have been reported, with less toxicity, with 5-fluorouracil plus folinic acid wi thout IFN-alpha. A larger Phase III study would be required to determi ne the value of IFN-alpha in this combination.