Primary G-CSF prophylaxis for adjuvant TC or FEC-D chemotherapy outside of clinical trial settings: a systematic review and meta-analysis

Variable febrile neutropenia (FN) rates reported with adjuvant TC (taxotereA (R), cyclophosphamide) and FEC-D (5-flurouracil, epirubicin, cyclophosphamide, docetaxel) outside of clinical trials have precluded definitive recommendations for primary G-CSF (granulocyte colony-stimulating factor) prophylaxis in most jurisdictions. A systematic review and meta-analysis was conducted to assess: (a) FN rates associated with TC and FEC-D without primary G-CSF prophylaxis outside of clinical trial settings, and (b) the potential impact of G-CSF prophylaxis on FN prevention. A MEDLINE search was conducted and major conference abstracts were reviewed up to June 15th 2011 to identify all relevant English-language studies. Random- and fixed-effects meta-analysis models were performed. Nine hundred two patients treated with TC and 1342 with FEC-D from 13 to 9 studies, respectively, were included. The pooled random-effects meta-analysis estimates of FN rates for TC and FEC-D without G-CSF were 29% (95% CI 24-35%) and 31% (95% CI 27-35%), with a 76% (RR = 0.24, 95% CI 0.14-0.41) and 63% (RR = 0.37, 95% CI 0.11-1.24) relative risk reduction with G-CSF, respectively. In routine clinical practice, TC and FEC-D without G-CSF are associated with FN rates exceeding the 20% threshold for which primary G-CSF prophylaxis is commonly recommended, and are considerably higher than those reported in pivotal clinical trials.