Abstract P3-15-01: Primary G-CSF Prophylaxis during the First Two Cycles Only or Throughout All Chemotherapy Cycles in Breast Cancer Patients at Risk of Febrile Neutropenia: Final Results from a Phase III Trial of the Dutch Breast Cancer Trialists Group (BOOG)

Abstract

Abstract Background: In patients at risk of febrile neutropenia (FN), the highest incidence of FN is seen during the first chemotherapy cycles. This observation questions the effectiveness of continued G-CSF prophylaxis during later chemotherapy cycles. Methods: We conducted a multicenter phase III study in breast cancer. Patients were randomized to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). Patients were eligible if treated with 3-weekly chemotherapy, being at risk of FN according to criteria of international guidelines. This was an equivalence study, aimed to include 230 patients, with FN as primary endpoint. Results: An independent Data Safety Monitoring Board recommended premature closure of the study because of an unacceptable increase in FN rate in the experimental arm. In total, 85 patients enrolled the experimental arm and 84 patients the standard arm till 15 th December 2009. Baseline characteristics were well belanced: age ≥65years in 93% versus 95%, ECOG PS of zero in 82% versus 88%, treated with docetaxel containing chemotherapy in (neo)-adjuvant setting in 97% versus 100%, respectively. At least one episode of FN was seen in 27 (32%) patients of the experimental arm compared with 4 (5%) patients in the standard arm (P<0.0001). Notably, in the experimental arm FN occurred predominantly in the third cycle, whereas in the standard arm FN was seen throughout all cycles. Fever, infection and/or mucositis led to serious adverse events in 31 (36%) patients in the experimental arm versus in 11 (13%) patients in the standard arm (P<0.001). In both arms, 5% of patients stopped or changed treatment because of toxicity. Most patients experienced only one FN episode. In these, chemotherapy was mostly given as planned, but in 61 % of patients with secondary G-CSF prophylaxis and in 21% of patients with secondary antibiotic prophylaxis (in the experimental arm). Conclusion: We conclude that in patients at risk of FN, primary G-CSF prophylaxis cannot be limited to the first chemotherapy cycles, despite the well known increased FN incidence in the first cycles without prophylaxis. With only 2 cycles protected, FN risk is increased in the third cycle. Support: The Netherlands organization for health research and development (ZonMw) and sanofi-aventis Netherlands B.V. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-15-01.