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.
CXCL12 rs1801157 polymorphism in patients with breast cancer, hodgkin's lymphoma, and non-hodgkin's lymphoma