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Standard Versus Intensified Chemotherapy With Granulocyte Colony-Stimulating Factor Support in Small-Cell Lung Cancer: A Prospective European Organization for Research and Treatment of Cancer–Lung Cancer Group Phase III Trial—08923

From the Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; University Medical Centre Nijmegen, Nijmegen; Vrije Universiteit Medical Centre, Amsterdam; Bosch Medicentrum, ‘s-Hertogenbosch; Ziekenhuis St Jansdal, Harderwijk; and Erasmus MC, Rotterdam, the Netherlands; Thoraxklinik Rohrbach, Heidelberg, Germany; PCK Maritime Hospital, Gdynia; and Medical University of Gdansk, Gdansk, Poland; and European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium.

Address reprint requests to Andrea Ardizzoni, MD, Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy; email: andrea.ardizzoni{at}istge.it

PURPOSE: To assess the impact on survival of increasing dose-intensity (DI) of cyclophosphamide, doxorubicin, and etoposide (CDE) in small-cell lung cancer (SCLC).

PATIENTS AND METHODS: Previously untreated SCLC patients were randomized to standard CDE (cyclophosphamide 1,000 mg/m² and doxorubicin 45 mg/m² on day 1, and etoposide 100 mg/m² on days 1 to 3 every 3 weeks, for five cycles) or intensified CDE (cyclophosphamide 1,250 mg/m² and doxorubicin 55 mg/m² on day 1, and etoposide 125 mg/m² on days 1 to 3 with granulocyte colony-stimulating factor [G-CSF] 5 µg/kg/d on days 4 to 13 every 2 weeks, for four cycles). Projected cumulative dose was almost identical on the two arms, whereas projected DI was nearly 90% higher on the intensified arm. Two hundred forty-four patients were enrolled. The first 163 patients were also randomized (2 x 2 factorial design) to prophylactic antibiotics or placebo to assess their impact on preventing febrile leukopenia (FL). This report focuses on chemotherapy DI results.

RESULTS: With a median follow-up of 54 months, 216 deaths have occurred. Actually delivered DI on the intensified arm was 70% higher than on the standard arm. Intensified CDE was associated with more grade 4 leukopenia (79% v 50%), grade 4 thrombocytopenia (44% v 11%), anorexia, nausea, and mucositis. FL and number of toxic deaths were similar on the two arms. The objective response rate was 79% for the standard arm and 84% for the intensified arm (P = .315). Median survival was 54 weeks and 52 weeks, and the 2-year survival rates were 15% and 18%, respectively (P = .885).

CONCLUSION: A 70% increase of CDE actual DI does not translate into an improved outcome in SCLC patients.

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