Schedule dependency of the combination methotrexate-vinblastine against human urothelial cancer grown in nude mice.
The combination of methotrexate (MTX) and vinblastine (VLB) was evaluated using different doses and treatment schedules in human transitional cell carcinoma line SW-1738, TCC-K1 and TR-49 grown in the nude mouse. Maximally tolerated weekly doses of MTX, 30 mg/kg, and VLB, 3 mg/kg, were given intraperitoneally for four consecutive weeks singly, concurrently, and separated by 24, 48 and 72 hour intervals. MTX-VLB drug sequence was not a factor in determining tumor regression or response rates when the second agent was administered 24 or 48 hours after the first agent. However, when VLB was administered 72 hours after MTX, a significant statistical difference (0.005 greater than p greater than 0.001) was observed for all tumor lines studied compared to either controls, simultaneous administration of both agents and/or VLB administered 24 or 48 hours after MTX. Additionally, dose reduction of either agent by 30% proved ineffective. Thus, tumor response to MTX-VLB combination was dependent both on schedule and dose. Application of this schedule dependency may be beneficial in management of urothelial tract tumors.
Kyriazis
A P
AP
Department of Pathology, New York Medical College, Valhalla.
Yagoda
A
A
Kyriazis
A A
AA
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage
D014747:Vinblastine; D008727:Methotrexate