In vitro antagonism between cisplatin and vinca alkaloids.

The effects of the combination of cisplatin and other cytotoxic agents were studied in vitro. When A549 lung cancer cells were treated simultaneously with cisplatin and other cytotoxic agents, cisplatin additively increased the cytotoxic effects of etoposide, mitomycin C, adriamycin, 5-fluorouracil and 1-beta-D-arabinofuranosylcytosine, but antagonised those of vincristine, vindesine, vinblastine and podophyllotoxin. The antagonism between cisplatin and vincristine was also observed with HT29 colon cancer cells. NC65 renal carcinoma cells and A431 epidermoid carcinoma cells when these cells were simultaneously exposed to both agents. When A549 cells were exposed to cisplatin and vincristine sequentially, the antagonism between them was evident when cells were pretreated with cisplatin but not when treated in the opposite sequence. Therefore, when combination chemotherapy including cisplatin and vinca alkaloids is given, possible antagonism between them should be considered, especially in determining the schedule of drug administration.