744 Methotrexate, L-folinic acid and 5-fluorouracil in the treatment of advanced digestive tract carcinomas

In a preliminary study we demonstrated that the dosage of MTX required to achieve a MTX serum level above 1 μM for at least 24 h was 500 mg/sqm i.v. A combination of MTX 500 mg/sqm i.v.(day 1), LFA 250 mg/sqm i. v. + 5FU 600 mg/sqm i. v. (day 2) every 2 wks in the treatment of 94 consecutive pts with advanced gastrointestinal malignancies was demonstrated as effective as other biochemical modulation of 5FU. In addition, a MTX serum level ≥ 2 μM seemed related to the probability of response. From Sept. 1994 to date, 48 pts affected by advanced carcinoma of the digestive tract were treated every 2 weeks for at least 4 courses with MTX 750 mg/sqm on d. 1, LFA 250 mg/sqm + 5FU 800 mg/sqm on d.2. Presently, 29 pts are evaluable for response. Primary site was large bowel in 22, stomach in 4, gall-bladder in 2, and pancreas in 1. Fourteen pts had received a previous systemic chemotherapy, mainly with fluoropyrimidine ± LFA. We obtained 1 CR and 5 PRs (OR 21%). Chemotherapy-naive pts showed an OR in 33% of cases (stomach 33%, colon-rectum 40%), while responses were reported in 7% of previously treated pts. The most common acute toxicities were mucositis (WHO G 3–4 in 6% of courses and 19% of pts), and leucopenia (5% and 15%).