BIOCHEMICAL MODULATION OF 5-FLUOROURACIL BY METHOTREXATE IN PATIENTS WITH ADVANCED GASTRIC-CARCINOMA

A phase II trial was conducted to evaluate the efficacy and toxicity o f a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with le ucovorin (LV) rescue) as first-line chemotherapy in patients with loca lly advanced (inoperable) or metastatic gastric carcinoma. From July 1 993 through August 1996, 36 patients with advanced gastric carcinoma r eceived a regimen that consisted of: MTX 200 mg/m(2) diluted in 250 mi normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m(2) intravenous push injection at hour 20. Beginning 24 hou rs after MTX administration all patients received LV 15 mg/m(2) intram uscularly every 6 hours for six doses. Cycles were repeated every 15 d ays. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%- 60%). One patient (3%) achieved complete response and 14 (40%) achieve d partial response. No change was recorded in 14 patients (40%) and pr ogressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death re sulting from severe leukopenia occurred. The dose-limiting toxicity wa s mucositis. Five episodes of grade 3 or 4 stomatitis were observed an d caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with adva nced gastric cancer. Further investigation both in experimental and cl inical fields is needed to clearly define its role and to design the b est modulatory strategy.