ESCALATED M-VAC CHEMOTHERAPY AND RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (RHGM-CSF) IN PATIENTS WITH ADVANCED UROTHELIAL TRACT TUMORS

Background: The M-VAC regimen (methotrexate, vinblastine, adriamycin, and cisplatin) has significant antitumor activity in patients with adv anced urothelial tract cancer. Growth factors may provide the possibil ity of treating patients with higher doses of chemotherapy, for longer periods, with less morbidity, and improved results. A trial of an esc alated dosage of M-VAC with recombinant GM-CSF (rhGM-CSF) was initiate d. Patients and methods: 23 patients were treated with an escalated do se of M-VAC every 2 weeks plus rhGM-CSF 250 micrograms/m2 s.c. days 4- 10. Dose level I (n = 13) was 1.65 times the dose of standard M-VAC. A driamycin and cisplatin were given at 2.5 times the dose of standard M -VAC. Dose level II (n = 10) was a relative dose intensity of 1.95. Ad riamycin and cisplatin were both given at 2.9 times the dose. Conclusi ons: The response rate was 70% (95% CI 60%-80). Seven patients (30%) h ad CR, and 9 (39%) had a PR. Five (22%) patients had stable disease an d 2 (9%) had progression. of the CR patients, 3 had the CR confirmed p athologically (CRp). Response occurred in 11 patients treated at dose level I and 5 at dose level II. Toxicity was primarily hematologic. Do se level II was too toxic due to thrombocytopenia. Non-hematologic tox icity was minimal. The value of this schedule (dose level I) compared to standard M-VAC will be further evaluated in a randomized trial to b e initiated by the Genitourinary Group of the EORTC.