IFOSFAMIDE, CARBOPLATIN, AND ETOPOSIDE - A NEW REGIMEN WITH A BROAD-SPECTRUM OF ACTIVITY

Purpose: To conduct a phase I/II evaluation of the combination of ifosfamide, carboplatin, and etoposide (ICE) to determine toxicity and activity in a variety of refractory malignancies. Patients and Methods: Two hundred four patients, 13 to 64 years of age, with a variety of malignancies, including refractory breast cancer and Hodgkin's and non-Hodgkin's lymphoma, were treated with two cycles of ICE, consisting of intravenous ifosfamide 2 g/m2, carboplatin 400 mg/m2, and continuous infusion etoposide 600 mg/m2 administered in divided doses over 2 days. The regimen was repeated at approximately 28-day intervals. Results: One hundred ninety-one patients (94%) received two cycles at full doses and were assessable for response and toxicity. Complete and partial responses were seen in breast cancer (20%, n = 93), non-Hodgkin's lymphoma (30%, n = 37), Hodgkin's disease (60%, n = 10), melanoma (9%, n = 11), a variety of sarcomas (20%, n = 10), and other malignancies (43%, n = 30). Myelosuppression was prominent, with significant neutropenia requiring frequent hospitalization for neutropenic fever, and thrombocytopenia and anemia requiring frequent platelet and RBC transfusions. However, the overall treatment-related mortality rate was only 3%. No other moderate to severe organ toxicity was seen at a frequency of greater than 1%. Conclusion: This regimen is active in a variety of refractory malignancies, with significant but tolerable hematologic toxicity. The addition of hematopoietic growth factors may allow further dose escalation.