Optimal administration schedules of the newly synthesized platinum analog NK121 and bleomycin analog NK313 in nude mice with squamous cell carcinoma.

Abstract

To determine the optimal administration schedules of the newly synthesized, less nephrotoxic platinum analog NK121 and less pneumotoxic bleomycin analog NK313, the antitumor effects of 2 different injection schedules, (1) single injections on days 1, 5, and 9, (2) continuous infusion for 7 days, were compared in nude mice bearing human squamous cell carcinoma. Tumor growth delay was employed as the experimental endpoint of antitumor activity. Body weight and hematologic changes in the mice were also investigated as indications of drug toxicity after the combination treatment of NK121 and NK313. The antitumor effects of the 2 analogs indicated higher responses with the single injections of NK121 and continuous infusion of NK313. In combination chemotherapy with NK121 and NK313, the highest antitumor effect was observed when mice were given NK121 by single injections followed by NK313 by continuous infusion. This sequence was also less toxic than a simultaneous treatment schedule, which was of weak clinical significance because of its low antitumor activity, severe weight loss, slight myelosuppression, and renal toxicity.