Phase 1 study of carboplatin in patients with advanced cancer, intermittent intravenous bolus, and 24-hour infusion.

We undertook a phase 1 study of Carboplatin (CBDCA) on an intermittent single intravenous (IV) bolus (schedule A) and a 24-hour continuous infusion schedule (schedule B). Hydration and forced diuresis were not performed. Patients were not premedicated for anticipated vomiting. Thirty-eight adult patients with solid tumors received a total of 71 courses. In schedule A, doses were escalated from 20 to 600 mg/m2. The dose-limiting toxicity was myelosuppression. At doses of 270 mg/m2 and higher, leukopenia and thrombocytopenia were reproducibly seen. The dose of 600 mg/m2 was the maximally tolerated dose, producing severe thrombocytopenia (platelet counts less than 30,000/microL). Other toxicities included a fall in hemoglobin levels and tolerable nausea and vomiting. Schedule B produced comparable hematologic and emetogenic toxicities to those in schedule A. In three patients audiograms became abnormal with high-frequency hearing loss without overt deafness. Two patients developed hypomagnesemia without irre...