Phase I clinical trial of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP).
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| Abstract |
cis-Dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP), a second-generation platinum complex with little or no nephrotoxicity in preclinical studies, has undergone phase I clinical testing and initial pharmacokinetic evaluation in 26 patients with solid tumors who received 40 courses of treatment. Doses of 20-350 mg/m2 were evaluated as single 2-hr infusions given every 3 weeks for two doses, with 2 L of pretreatment hydration (but no diuretics) in all but five patients. Nausea and vomiting was almost universal but was severe in only three courses. The dose-limiting toxic effect was myelosuppression, with a median wbc count nadir of 2500/mm3 and a median platelet count nadir of 32,000/mm3 at the maximum tolerated dose of 350 mg/m2. No increase in serum creatinine or decrease in creatinine clearance was seen. No pretreatment hydration was given in five of the seven patients treated at 350 mg/m2. Two cases of hypersensitivity were seen. No hearing loss was observed and no other toxic effects were noted. Plasma decay of total platinum was biexponential with a prolonged beta phase. Recovery of platinum in the urine was rapid up to 8-10 hrs and slow thereafter. Recoveries were incomplete and variable (16.5%-62% of the dose at 48 hrs).
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| Authors | P J Creaven, S Madajewicz, L Pendyala, A Mittelman, E Pontes, M Spaulding, S Arbuck, J Solomon |
| Journal | Cancer treatment reports (Cancer Treat Rep) Vol. 67 Issue 9 Pg. 795-800 (Sep 1983) ISSN: 0361-5960 [Print] United States |
| PMID | 6883356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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