Phase I study of cis-dichloro-trans-dihydroxy-bis(isopropylamine)platinum IV (CHIP)

Cis-dichloro-trans-dihydroxy-bis(isopropylamine)platinum IV (CHIP) is a second-generation cis-platinum (DDP) derivative with an octahedral conformation of the platinum complex, far more water-soluble than DDP. Tests in numerous murine tumor systems demonstrate a spectrum of activity similar to that of DDP. A phase I study of CHIP using 5 consecutive daily 1-hour infusions without pretreatment hydration or diuretics was completed at Hospital Paul-Brousse, Villejuif, France. 16 patients received a total of 28 courses of CHIP. In 11 of them hematologic toxicity could be assessed. The starting dose, 20 mg/m2/day X 5, was increased to 30, 45 and 50 mg/m2. There was neither renal nor neurotoxicity. Nausea and vomiting were constant but usually mild or moderate. No diarrhea was seen. Myelosuppression was dose-limiting with a mean polymorphonuclear cell (PMN) count nadir of 2.4 X 10(3)/mm3 (range 1 X 10(3)-3 X 10(3)/mm3) and a mean platelet count nadir of 110 X 10(3)/mm3 (range 60 X 10(3)-180 X 10(3)/mm3) at the recommended dosage of 45 mg/m2/day X 5. The drug should be given every 6 weeks because of the late platelet nadir. A total of 13 patients are evaluable for efficacy. One histologically documented complete response lasting more than 12 months was observed in a patient with an ovarian carcinoma.