title: The effect of dose intensity on M-VAC therapy for advanced urothelial cancer.
abstract: M-VAC therapy (methotrexate, vinblastine, Adriamycin, and cisplatin) has improved the treatment results of urothelial cancer patients. However, it is sometimes complicated by drug toxicities, including bone marrow suppression. We analyzed the relative dose intensity in each patient undergoing M-VAC chemotherapy in relation to the chemotherapeutic effect and survival. In addition, the role of granulocyte colony-stimulating factor (G-CSF) in the dose intensity of M-VAC therapy was analyzed. Between June 1988 and March 1993, 29 patients with advanced urothelial cancer were treated with M-VAC therapy in our institution. Of 18 patients with evaluable lesions, 2 (11.1%) showed a complete response (CR) and 7 (38.9%) showed a partial response (PR), and the overall response rate was 50.0%. The median follow-up period for these 18 patients was 14.6 months and the median survival was 8.7 months, with 12 of the 18 patients being alive at the time of analysis. The relative dose intensity (RDI) for these 18 patients was 0.81 for methotrexate, 0.80 for vinblastine, 0.92 for Adriamycin, and 0.91 for cisplatin, for a mean RDI of 0.87. There was no correlation between the chemotherapeutic effect and the RDI. When we calculated the RDI for all 29 patients who underwent M-VAC therapy, G-CSF increased the RDI of Adriamycin significantly. The results of this retrospective study indicate that a dose intensity for M-VAC therapy in the range of 0.61-1.00 is unlikely to correlate with the chemotherapeutic effect, although G-CSF contributes to increasing the RDI of Adriamycin.
authors.affiliation: Department of Urology, University of Tsukuba, Ibaraki, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Miyanaga
authors.forename: H
authors.initials: H
authors.lastname: Akaza
authors.forename: T
authors.initials: T
authors.lastname: Shimazui
authors.forename: M
authors.initials: M
authors.lastname: Ohtani
authors.forename: K
authors.initials: K
authors.lastname: Koiso
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality; D007682:Kidney Pelvis; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D015996:Survival Rate; D014516:Ureteral Neoplasms / Q000188:drug therapy / Q000401:mortality; D014523:Urethral Neoplasms / Q000188:drug therapy / Q000401:mortality; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate