Phase I clinical trial of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP).
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).
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
D009944:Organoplatinum Compounds; C023359:iproplatin