Use of high-dose etoposide/ifosfamide/carboplatin/epirubicin and peripheral blood progenitor cell transplantation in limited-disease small cell lung cancer.

Conventional-dose chemotherapy for limited-disease small cell lung cancer has resulted in high response rates, but rarely in a cure. In an ongoing phase I-II trial, limited-disease small cell lung cancer patients received high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation as part of an early intensification strategy after two cycles of induction chemotherapy. Eligible patients (n = 18) were initially treated with two cycles of etoposide (500 mg/m2), ifosfamide (4 g/m2), cisplatin (50 mg/m2), epirubicin (50 mg/m2) and granulocyte colony-stimulating factor to combine an effective, standard-dose chemotherapy regimen with simultaneous mobilization of PBPCs. Patients who were in partial remission or complete remission after two cycles of induction chemotherapy received high-dose intensification chemotherapy with cumulative doses of 1,500 mg/m2 etoposide, 12 g/m2 ifosfamide, 750 mg/m2 carboplatin, and 150 mg/m2 epirubicin, followed by autologous PBPC transplantation and granulocyte colony-stimulating factor. The duration of the complete chemotherapy program was 9 weeks. All patients received chest irradiation posttransplantation (50 Gy), and those in complete remission received additional prophylactic cranial irradiation (30 Gy). To date, 13 patients with a median age of 49 years (age range, 34 to 62 years) have been treated within this combined-modality treatment protocol. At a median follow-up of 14 months (range, 3 to 45 months) after transplantation, 11 patients were alive and nine were still in complete remission. Nonhematologic toxicity was acceptable; World Health Organization grades 2 to 4 oral mucositis was the most frequently observed (85%) adverse event. No toxic deaths were observed, and hematopoietic reconstitution occurred rapidly after PBPC transplantation; platelet transfusion independence (> 20,000 microL) and neutrophil counts greater than 500 microL were observed at study day 12+. The median survival time was not yet reached. These preliminary data demonstrate that early, high-dose chemotherapy and PBPC transplantation followed by local radiotherapy is safe and may lead to prolonged disease-free survival in some patients. Prospective, randomized studies in a larger series of patients will be required to provide definitive proof of the role of early high-dose chemotherapy in the management of limited-disease small cell lung cancer.