[Development of carboplatin]

Carboplatin (CBDCA; commercial name: Paraplatin) is a platinum complex having 1-cyclobutanedicarboxylic acid group at the two chlorine positions of cisplatin (CDDP). In the preclinical studies, CBDCA was proved to be almost equally effective to various murine tumors compared to cisplatin. Compared to cisplatin, of which free platinum was not detected from 2 hr after administration, the free type of more than 85% of total platinum concentration remained in the blood even 8 hrs after administration. Total urine excretion at 2-4 hrs after administration of CBDCA was about 57-82%, indicating CBDCA's relative rapid urine excretion compared to CDDP. In the clinical trials in Japan, appreciable clinical responses were observed in head and neck, small cell lung, ovarian, uterine cervical cancers, testicular tumor and malignant lymphoma. The renal toxicity was considerably slight, resulting in almost no hydration during treatment. Nausea and vomiting were also slight and there were no hearing-loss and neurotoxicities. The dose-limiting factor (DLF) in the phase I study was myelosuppression. From these results, it was found that carboplatin's antitumor efficacies were almost identical with cisplatin and much less toxic than cisplatin. Carboplatin will serve as a useful antitumor drug in current cancer chemotherapy.