Summary
Iproplatin [cis-dichlor-trans-dihydroxy-bis-isopropylamine platinum (CHIP, JM9)] is a new antineoplastic platinum analogue with an octahedral conformation. It has more water solubility than does cisplatin and was found to have less neurotoxicity and nephrotoxicity in experimental animals than cisplatin. Like cisplatin, it has been demonstrated to have a broad spectrum of activity in experimental tumor systems. A phase I study of iproplatin was conducted in 28 patients (12 with melanoma, 8 with sarcoma, 6 with breast cancer, and 2 with colon cancer). All patients had failed prior chemotherapy. Four consecutive doses of iproplatin were administered at weekly intervals followed by a rest period of two weeks for hematologic recovery (one course). One hundred forty-two weekly doses were administered with all patients except three receiving at least one full course. The weekly starting dose of 40 mg/m2 was increased to 120 mg/m2 given over 30 minutes without hydration. Myelosuppression predominantly thrombocytopenia, was the dose-limiting toxicity at weekly doses of ≥ 95 mg/m2 per course. With iproplatin doses 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median granulocyte counts were 2.6 × 103/mm3, 2.2 × l03/mm3, and 1.8 × 103/mm3, respectively. Similarly, at iproplatin doses of 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median platelet counts were 144 × 103/mm3, 99 × 103/mm3, and 31 × 103/mm3, respectively. Mild to moderate nausea and vomiting were observed in the majority of patients. No significant neurotoxicity, nephrotoxicity, or ototoxicity was observed. Objective tumor regression was not observed in this study. The toxicity pattern of this schedule was not found to be significantly different from other schedules reported. If this schedule is pursued for phase II studies, a dose of 95 mg/m2/week x 4 repeated at 6-week intervals will be the recommended doses in patients who have been previously treated.
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Presented in Part at the American Society of Cancer Research, 1983. Supported in Part by Bristol-Myers Company
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Chawla, S.P., Yap, BS., Tenney, D.M. et al. Phase I study of weekly-administered iproplatin [cis-dichloro-trans-dihydroxy-bis-isopropylamine platin (chip, JM9)]. Invest New Drugs 6, 311–317 (1988). https://doi.org/10.1007/BF00173650
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DOI: https://doi.org/10.1007/BF00173650