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

The in vivo combination effect of navelbine (NVB, KW-2307) plus cisplatin 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 their combination on various schedules when the interval of administrations was within 24 h. Against i.v. inoculated P388 leukemia, the most significant combination effect was observed when cisplatin was administered 4 h after NVB injection (ILS(%) > 451) and three long-term survivors were observed. On this schedule, the combination of LD10 of each drug was achieved, indicating the lack of addition of toxicity. This was further proved by examination of body weight change, white blood cell count and platelet count. interestingly, significant elevation of blood urea nitrogen concentration by cisplatin was prevented by the combination with NVB. The combination of maximum tolerated dose of NVB and cisplatin was also tolerable in nude mice, and their combination effect was observed against human lung large cell carcinoma Lu-65 and adenocarcinoma PC-12. The number of toxic death mice was more in VDS plus cisplatin-treated groups than in NVB plus cisplatin-treated groups, indicating that the combination chemotherapy of NVB plus cisplatin is a better regimen than that of VDS plus cisplatin in experimental tumor systems.