MODIFIED THERAPY WITH 5-FLUOROURACIL, DOXORUBICIN, AND METHOTREXATE IN ADVANCED GASTRIC-CANCER

Background. In an attempt to decrease the toxic effects of fluorouraci l, doxorubicin, and methotrexate (FAMTX) by reducing the dose of metho trexate from 1500 mg/m2, according to the original regimen, to 1000 mg /m2, the authors designed the modified FAMTX treatment that was evalua ted in a prospective Phase II-III randomized trial. Methods. Patients with advanced gastric cancer were randomized to receive modified FAMTX treatment or supportive measures only (control group). In the middle of the study, the randomization was interrupted because of strong evid ence of benefit in terms of tumor reduction and projected survival in the treatment arm receiving chemotherapy. By the end of the study, 30 assessable patients had received chemotherapy and 10 had received supp ortive treatment. Results. The overall response rate was 50% (15 patie nts); 12 patients (40%) had partial responses and 3 (10%) had complete responses (CR). One patient with extensive peritoneal carcinomatosis attained a CR pathologically documented by laparoscopic examination an d peritoneal biopsy. The median overall survival time of the treated g roup was 9 months, whereas that of the control group was only 3 months (P = 0.001). The median overall survival time of the responders was 1 6 months, and their median remission duration was 8 months. The regime n was well tolerated, with a very acceptable toxicity profile. There w as one toxic death resulting from neutropenia and sepsis in a patient who did not receive adequate leucovorin rescue. Conclusions. This regi men appears to prolong survival in patients with advanced gastric canc er, and the reduction of the methotrexate dose does not seem to compro mise its efficacy.