COMBINATION EFFECT OF NAVELBINE (VINORELBINE DITARTRATE) WITH CISPLATIN AGAINST MURINE-P388 LEUKEMIA AND HUMAN LUNG-CARCINOMA XENOGRAFTS INMICE

The in vivo combination effect of navelbine (NVB, KW-2307) plus cispla tin was compared with that of vindesine (VDS) plus cisplatin in terms of antitumor activity and side effects. The antitumor activity of NVB or cisplatin against i.p. inoculated P388 leukemia was augmented by th eir combination on various schedules when the interval of administrati ons was within 24 h. Against i.v. inoculated P388 leukemia, the most s ignificant combination effect was observed when cisplatin was administ ered 4 h after NVB injection (ILS(%) > 451) and three long-term surviv ors were observed. On this schedule, the combination of LD10 of each d rug was achieved, indicating the lack of addition of toxicity. This wa s further proved by examination of body weight change, white blood cel l count and platelet count. interestingly, significant elevation of bl ood urea nitrogen concentration by cisplatin was prevented by the comb ination with NVB. The combination of maximum tolerated dose of NVB and cisplatin was also tolerable in nude mice, and their combination effe ct was observed against human lung large cell carcinoma Lu-65 and aden ocarcinoma PC-12. The number of toxic death mice was more in VDS plus cisplatin-treated groups than in NVB plus cisplatin-treated groups, in dicating that the combination chemotherapy of NVB plus cisplatin is a better regimen than that of VDS plus cisplatin in experimental tumor s ystems.