Phase I study of a combination chemotherapy of nedaplatin and cisplatin

A new platinum complex, nedaplatin, has been reported to be effective for both ovarian and cervical cancers. We designated a phase I dose-escalation study of a combination chemotherapy of nedaplatin and cisplatin to investigate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Six patients, including two with advanced cervical cancer, three with ovarian clear cell adenocarcinoma and one with endometrial clear cell adenocarcinoma, were enrolled in this study. The doses of the two agents were escalated alternatively, i.e., a tandem method, from 40 to 80 mg/m2 by 20 mg/m2. Nedaplatin and cisplatin were administrated by intravenous drip infusion and repeated after an interval of at least 4 weeks, as a rule. The major toxicity observed was hematotoxicity. One of the 6 patients dropped out of this study because of severe hematotoxicity after 80 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin were administered. With a dose of 80 mg/m2 nedaplatin and 80 mg/m2 cisplatin, severe neutropenia was found in all 6 patients, and thrombocytopenia and anemia were found in 1 patient, respectively. A slight hearing loss was detected by audiometry in 5 patients, but no one was inconvenienced in daily life. Mild nausea and vomiting were also observed in all 6 patients. In conclusion, the DLT of this combination therapy was hematotoxicity and the MTD was 80 mg/m2 for nedaplatin and 60 mg/m2 for cisplatin, respectively. Thus, 60 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin may be recommended for combined administration.