Cisplatin and nifedipine: synergistic antitumor effects against an inherently cisplatin-resistant tumor.

Resistance to cisplatin is a relative term and is at least partially attributable to its narrow therapeutic index. It is often not possible to successfully treat tumors exhibiting even a small inherent resistance to cisplatin by increasing the dose level of cisplatin, because such therapies may be fatally toxic to a patient. Thus, combination therapy with an agent which enhances cisplatin's antitumor effects with little or no enhancement of cisplatin's toxicities, may be of value in the treatment of human tumors which fail to respond to treatment with cisplatin alone. We recently reported that nifedipine, a dihydropyridine class calcium channel blocker, enhances the antitumor actions of cisplatin against a cisplatin-sensitive murine amelanotic melanoma. We now report that nifedipine enhances cisplatin's antitumor effects against a murine carcinoma (Lewis lung carcinoma) that is inherently resistant to cisplatin.