Background: In an attempt to decrease the toxic effects of fluorouracil, doxorubicin, and methotrexate (FAMTX) by reducing the dose of methotrexate from 1500 mg/m2, according to the original regimen, to 1000 mg/m2, the authors designed the modified FAMTX treatment that was evaluated 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 evidence 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 supportive treatment.
Results: The overall response rate was 50% (15 patients); 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 and peritoneal biopsy. The median overall survival time of the treated group 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 16 months, and their median remission duration was 8 months. The regimen was well tolerated, with a very acceptable toxicity profile. There was one toxic death resulting from neutropenia and sepsis in a patient who did not receive adequate leucovorin rescue.
Conclusions: This regimen appears to prolong survival in patients with advanced gastric cancer, and the reduction of the methotrexate dose does not seem to compromise its efficacy.