Sequence-dependent toxicity profile in modified FAMTX (fluorouracil-adriamycin-methotrexate) chemotherapy with...

For advanced irresectible gastric cancer, sequential high-dose methotrexate and 5-fluorouracil (both on day 1) combined with adriamycin on day 15 (FAMTX regimen), cycled every 28 days, is a fairly effective but toxic treatment, with a high incidence of neutropenic fever, dose reductions and dose delays. In order to improve FAMTX toxicity, we studied the feasibility of two modified FAMTX regimens with lenograstim support. Seven advanced gastric cancer patients were treated with all three FAMTX drugs on day 1 followed by lenograstim 150 microgm(-2)for 10 days, in 21-day cycles (FUMA regimen). The next seven patients were treated with the same drugs at the same doses, but with adriamycin 1 day prior to methotrexate and 5-fluorouracil administration (AFUM regimen). Patients were monitored for toxicity, response, and survival. 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, considerable toxicity consisting of mucositis and fatigue as well as grade 4 neutropenia occurred, and forced four out of seven patients to stop treatment. The consecutive AFUM regimen showed only mild toxicity, and all patients could finish treatment without dose reductions or delays. We found unanticipated and probably sequence-dependent toxicity profiles in two investigational, modified FAMTX schedules with lenograstim support, leading to high rates of dose-limiting toxicity in the FUMA regimen as opposed to mild toxicity in the AFUM regimen, even though the same total drug doses and treatment cycle length (dose intensity) were employed.