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.
D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D051381:Rats; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C023359:iproplatin