High Dose Cisplatin: Modulation of Toxicity

摘要: Dose escalation of cisplatin is theoretically attractive due to the steep dose-response curve for antitumor activity. However, relationship toxicity appears be equally steep. A high dose regimen 40 mg/m2 5 days in 3% saline (200 mg/m2/28 day cycle) results limiting peripheral neuropathy and myelosuppression, associated with accumulation ultrafiltrate platinum species. pharmacokinetically designed delivering same projected intensity on a divided schedule (100 1 8) avoids accumulation. In phase II study non-small cell lung cancer (NSCLC), this resulted reduced incidence severity absence severe myelosuppression. At mean cumulative 525 mg/m2/patient, delivered was 94% (47.2 mg/m2/week). An encouraging response rate median survival time NSCLC were also observed, suggesting positive clinical impact enhanced intensity. subsequent SWOG comparing 8 metastatic melanoma confirmed latter schedule. Nephrotoxicity ototoxicity similar both groups, but myelosuppression neurotoxicity confined patients