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 irreversible renal dysfunction. Patients with poor performance status, preexisting renal dysfunction, a third fluid space, or bone metastases seemed to develop increased hematologic toxicity. The recommended phase 2 dose for good risk patients is 400 mg/m2 IV bolus and for poor risk patients 270 mg/m2 IV bolus. Responses were seen in one patient each with head and neck carcinoma (partial response), small cell lung cancer (minor response), and breast cancer (minor response).
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D016190:Carboplatin; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008274:Magnesium / Q000097:blood; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013921:Thrombocytopenia / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D003404:Creatinine; D016190:Carboplatin; D008274:Magnesium