HIGH-DOSE CARBOPLATIN AND RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN ADVANCED-STAGE RECURRENT OVARIAN-CANCER

Purpose: We investigated whether carboplatin myelosuppression could be favorably modulated by the administration of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in patients with advanced-stage ovarian cancer. Patients and Methods: Thirty-four patients with advanced-stage recurrent ovarian cancer were treated with high-dose carboplatin (800 mg/m2 per 35-day cycle) and rGM-CSF. rGM-CSF was administered as a daily subcutaneous injection starting 72 hours after the carboplatin dose and continuing until 7 days beyond the WBC nadir. rGM-CSF was administered in a phase I fashion. Seven patients were treated at an rGM-CSF dose of 3 μg/kg, 11 at 5 μg/kg, 10 at 10 μg/kg, and six at 20 μg/kg. Results: rGM-CSF-related toxicities that were not dose-related included nonneutropenic fever, rib pain, acute hypersensitivity reaction, and pericarditis. At the rGM-CSF dose of 20 μg/kg, debilitating malaise was seen in four of six patients and this was the dose-limiting tox-icity. Patient tolerance of the 3-μg/kg and 5-μg/kg doses was good, but tolerance was limited for the 10-μg/kg dose. Febrile neutropenia was seen in four of seven patients at 3 μg/kg, two of 11 at 5 μg/kg, two of 10 at 10 μg/kg, and one of six at 20 μg/kg. Cumulative carboplatin myelotoxicity was blunted only in respect to WBC count, and not for platelets or RBCs. Gastrointestinal bleeding was seen in seven patients. The administered dose-intensity of carboplatin averaged 134 mg/m2/wk for the cohort, or 670 mg/m2 per 35-day cycle. There were two clinical complete responses and eleven partial responses, for a response rate of 38%. Conclusion: rGM-CSF appears to be effective and tolerable at 5 μg/kg/d administered subcutaneously, if given with carboplatin doses up to approximately 600 mg/m2 over 35 days. The use of rGM-CSF with high-dose carboplatin is associated with a substantial response rate in poor-prognosis ovarian cancer patients.