High-dose cis-diamminedichloro-platinum therapy in patients with advanced breast cancer: pharmacokinetics, toxicity, and therapeutic efficacy.

Seventeen patients with advanced breast cancer were treated with cis-diamminedichloroplatinum (DDP) 100 mg per m2 every 21--28 days. Hydration and mannitol or furosemide diuresis was given. Responses were seen in two patients (one complete, one objective) with soft-tissue metastases. There was no difference in peak plasma platinum concentration (3.91 micrograms/ml +/- 1.41 micrograms/ml), terminal plasma half-life (116--288 hours), peak concentration of unbound platinum (0.7 micrograms/ml), or 24-hour urinary platinum excretion (6.7--17.2% of administered dose) between the objective responder and the nonresponders. Toxicities included severe nausea and vomiting, renal insufficiency, high-frequency hearing loss, and peripheral neuropathies. Hematologic toxicity was mild in most patients. DDP has limited activity when used as a single agent in this dose and schedule in patients with metastatic breast cancer.