1. 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
- Author
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Ardizzoni, A., Tjan-Heijnen, V.C., Postmus, P.E., Buchholz, E., Biesma, B., Karnicka-Mlodkowska, H., Dziadziuszko, R., Burghouts, J.T.M., Meerbeeck, J.P. van, Gans, S., Legrand, C., Debruyne, C., Giaccone, G., and Manegold, C.
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Cyclophosphamide ,medicine.medical_treatment ,Gastroenterology ,Small-cell carcinoma ,Statistics, Nonparametric ,Experimental diagnostics and therapy of malignancies ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Prospective Studies ,Carcinoma, Small Cell ,Lung cancer ,Survival rate ,Etoposide ,Aged ,Proportional Hazards Models ,Chemotherapy ,Dose-Response Relationship, Drug ,Cumulative dose ,business.industry ,Leukopenia ,Antibiotic Prophylaxis ,Middle Aged ,medicine.disease ,Surgery ,Granulocyte colony-stimulating factor ,Europe ,Survival Rate ,Treatment Outcome ,Oncology ,Doxorubicin ,Female ,business ,medicine.drug - Abstract
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 × 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.
- Published
- 2002