P5-20-04: Is Primary Prophylaxis with G-CSF Indicated for Adjuvant TC or FEC-D Chemotherapy? A Systematic Review and Meta-Analyses.

Abstract Background Adjuvant chemotherapeutic regimens incorporating docetaxel, including TC (taxotere 75 mg/m2; cyclophosphamide 600 mg/m2 q 3 weekly for 4 cycles) and FEC-D (5-flurouracil 500 mg/m2; epirubicin 100 mg/m2; cyclophosphamide 500 mg/m2 q 3 weekly for 3 cycles followed by docetaxel 100 mg/m2 q 3 weekly for 3 cycles), appear to be associated with rates of febrile neutropenia (FN) in routine clinical practice that are higher than those reported in the pivotal clinical trials (7-33% vs. 11% & 18–35% vs. 5%, respectively). Although primary prophylaxis with G-CSF (granulocyte colony-stimulating factor) is indicated for chemotherapeutic regimens associated with rates of FN > 20%, the variable FN rates reported with TC and FEC-D outside of clinical trials have precluded definitive recommendations for G-CSF primary prophylaxis in most jurisdictions. A systematic review and meta-analysis was therefore conducted to assess; i) FN rates associated with TC and FEC-D without and with G-CSF primary prophylaxis outside of clinical trial settings, and ii) the potential impact of G-CSF prophylaxis on FN prevention. Methods: A PubMed search was conducted and major conference abstracts were reviewed up to June 15th 2011 to identify all English language reports of FN rates associated with adjuvant TC or FEC-D outside of clinical trial settings. FN rates with and/or without G-CSF prophylaxis were abstracted, and LOS (length of stay in hospital) and mortality following FN were noted. Summary incidences and odds ratios (OR) with 95% confidence intervals (95%CI) were calculated using random- and fixed-effects models. Results: A total of 902 patients treated with TC (average age 55 years, range 27–84, 19% ≥ 65 years) and 1342 treated with FEC-D (average age 52 years, range 24–78, 9% ≥ 65 years) from 13 and 9 relevant studies respectively, were included. Overall FN rates of 17% (range: 7–33%) and 24% (range: 18–35%) were reported for TC and FEC-D, with an average primary G-CSF utilization rate of 47% and 30%, respectively. For TC, the pooled random-effects meta-analysis estimates of FN rates were 7% (95%CI: 5–10%) with primary G-CSF and 29% (95%CI: 24–35%) without G-CSF (OR=0.17, 95%CI: 0.09−0.33). For FEC-D, the FN rates were 9% (95%CI: 4–19%) with and 31% (95%CI: 27–35%) without primary prophylaxis (OR=0.22, 95%CI: 0.09−0.56). For FEC-D, 50% of the FN events occurred during the 1st D cycle and 65% overall occurred during D treatments. Older age (≥ 65 years) did not appear to correlate with higher FN rates. Breakthrough FN occurred in 5% across both regimens despite G-CSF secondary prophylaxis. FN was associated with 3.7 and 4.0 LOS days and 0% and 2% mortality during TC and FEC-D, respectively. Conclusions: TC and FEC-D without G-CSF are associated with unacceptably high FN rates in routine clinical practice. Primary prophylaxis with G-CSF should be considered for adjuvant TC chemotherapy, and for the D-component of FEC-D regimen, irrespective of patient age. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-04.

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