DOUBLE-MODULATION OF 5-FLUOROURACIL BY METHOTREXATE AND LEUCOVORIN INADVANCED COLORECTAL-CARCINOMA

A phase II trial was performed to evaluate the efficacy and toxicity o f a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) a nd leucovorin (LV) as first line chemotherapy in advanced colorectal c arcinoma. Between January 1990, and April 1992, 42 patients with metas tatic or advanced recurrent (inoperable) colorectal cancer were entere d into the study. Therapy consisted of a sequential combination of MTX , LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 min utes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 o ver 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 1 5 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeate d every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective re gression (OR) was observed in 14 of 38 patients (37%, 95% confidence i nterval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was obs erved. Double modulation of 5-FU with MTX and low dose of LV is an act ive regimen against advanced colorectal carcinoma and represents a pro mising strategy that should be further explored.