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Multiple Courses of High-Dose Ifosfamide, Carboplatin, and Etoposide With Peripheral-Blood Progenitor Cells and Filgrastim for Small-Cell Lung Cancer: A Feasibility Study by the European Group for Blood and Marrow Transplantation

From the Centre Pluridisciplinaire d'Oncologie, Lausanne, and ForMed, Statistics for Medicine, Evolène, Switzerland; Ospedale Civile, Ravenna, and Ospedale Civile Maggiore, Verona, Italy; Hopital Universitaire St-Luc, Brussels, and Centre Hospitalier Regional Citadelle, Liège, Belgium; and K. Dluski Hospital, Wroclaw, Poland.

Address reprint requests to Serge Leyvraz, MD, Centre Pluridisciplinaire d'Oncologie, CHUV BH 10, Rue du Bugnon 46, 1011 Lausanne, Switzerland; email serge.leyvraz{at}chuv.hospvd.ch

PURPOSE: To determine the feasibility and safety of multiple sequential courses of high-dose chemotherapy and peripheral-blood progenitor cells (PBPCs) administered in a multicenter setting to patients with small-cell lung cancer.

PATIENTS AND METHODS: Sixty-nine patients (limited disease, n = 30; extensive disease, n = 39) treated at 15 European centers were scheduled to receive three courses of high-dose chemotherapy with ifosfamide 10 g/m², carboplatin 1200 mg/m², and etoposide 1200 mg/m² (ICE) divided over 4 days at 28-day intervals. PBPCs were harvested before treatment and mobilized with epirubicin 150 mg/m² administered via an intravenous bolus divided over 2 days and filgrastim 5 µg/kg/d administered subcutaneously.

RESULTS: The performed leukaphereses (one to five per patient) yielded a median of 16.6 x 10⁶/kg (range, 1.0 to 96.6 x 10⁶/kg) CD34⁺ cells, which was sufficient for three reinfusions. Fifty patients (72%) completed the treatment according to schedule. Nine patients completed two courses, and six patients completed one course of treatment. The increase in dose-intensity was 290% that of a standard ICE regimen. The median duration of myelosuppression was similar between courses, namely 4 days (range, 1 to 12 days) for leukocytes less than 0.5 x 10⁹/L and 4 days (range, 0 to 22 days) for thrombocytes less than 20 x 10⁹/L. Febrile neutropenia developed in 66% of courses, severe diarrhea in 14%, mucositis in 10%, and nausea and vomiting in 21% of courses. There were six cases of toxic death (9%), most of which occurred in the first year of accrual and thus were attributable to the learning curve. The antitumor effect of the regimen was reflected in an 86% remission rate (95% confidence interval [CI], 74% to 93%), with 51% of patients achieving a complete response (95% CI, 38% to 63%). Median overall survival was 18 months for patients with limited disease and 11 months for patients with extensive disease.

CONCLUSION: This multiple sequential high-dose ICE regimen could be safely administered on a multicenter basis to patients with small-cell lung cancer. The dose-intensity could be increased to 290% that of standard ICE regimen. The benefit of this approach is currently being tested in a randomized trial that aims to double the long-term rate of survival for patients with small-cell lung cancer.

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