Sequence-dependent toxicity profile in modified FAMTX (fluorouracil-adriamycin-methotrexate) chemotherapy with lenograstim support for advanced gastric cancer: A feasibility study

For advanced irresectible gastric cancer, sequential high-dose methotrexate and 5-fluorouracil (both on day 1) combined with adriamycin on day 15 (FAM TX regimen), cycled every 28 days, is a fairly effective but toxic treatmen t, with a high incidence of neutropenic fever, dose reductions and dose del ays. In order to improve FAMTX toxicity, we studied the feasibility of two modified FAMTX regimens with lenograstim support. Seven advanced gastric ca ncer patients were treated with all three FAMTX drugs on day 1 followed by lenograstim 150 mu g m(-2) for 10 days, in 21-day cycles (FUMA regimen). Th e next seven patients were treated with the same drugs at the same doses, b ut with adriamycin 1 day prior to methotrexate and 5-fluorouracil administr ation (AFUM regimen). Patients were monitored for toxicity, response, and s urvival. The total number of courses was 27 for FUMA and 35 for AFUM with a median of four courses per patient in each cohort. In the FUMA regimen, co nsiderable toxicity consisting of mucositis and fatigue as well as grade 4 neutropenia occurred, and forced four out of seven patients to stop treatme nt. The consecutive AFUM regimen showed only mild toxicity, and all patient s could finish treatment without dose reductions or delays. We found unanti cipated and probably sequence-dependent toxicity profiles in two investigat ional, modified FAMTX schedules with lenograstim support,leading to high ra tes of dose-limiting toxicity in the FUMA regimen as opposed to mild toxici ty in the AFUM regimen. even though the same total drug doses and treatment cycle length (dose intensity) were employed. (C) 2000 Academic Press.