Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

Purpose Febrile neutropenia (FN) is a major complication of chemotherapy. Antibiotics as well as granulocyte colony-stimulating factor (G-CSF) are effective in preventing FN. This multicenter randomized phase III trial determines whether the addition of G-CSF to antibiotic prophylaxis can further reduce the incidence of FN in patients with small-cell lung cancer (SCLC) at the risk of FN. Patients and Methods Patients (N = 175) were stratified for stage of disease, performance status, age, and prior chemotherapy treatment, and were randomly assigned for treatment with cyclophosphamide, doxorubicin, and etoposide (CDE), followed by prophylactic antibiotics alone (ciprofloxacin and roxithromycin) or by antibiotics in combination with G-CSF on days 4 to 13. Results In cycle 1, 20 patients (24%) in the antibiotics group developed FN compared with nine patients (10%) in the antibiotics plus G-CSF group (P = .01). In cycles 2 to 5, the incidences of FN were practically the same in both groups (17% v 11%). Only the treatment parameters (odds ratio, 0.33; 95% CI, 0.14 to 0.78) and age (1.067 per year; 95% CI, 1.013 to 1.0124) were related to the probability of FN in cycle 1. Conclusion Primary G-CSF prophylaxis added to primary antibiotic prophylaxis is effective in reducing FN and infections in SCLC patients at the risk of FN with the first cycle of CDE chemotherapy. For patients with similar risk of FN, the combined use of prophylactic antibiotics plus G-CSF can be considered, specifically in the first cycle of chemotherapy.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2002.02.069 ◽

2002 ◽

Vol 20 (19) ◽

pp. 3947-3955 ◽

Cited By ~ 84

Author(s):

Andrea Ardizzoni ◽

Vivianne C.G. Tjan-Heijnen ◽

Pieter E. Postmus ◽

Erica Buchholz ◽

Bonne Biesma ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Phase Iii ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Small Cell Lung ◽

The Impact ◽

Stimulating Factor

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.

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