Prophylactic growth factor (GF) support with adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) for node-negative breast cancer (BC): An interim safety analysis of the GEICAM 9805 study

Abstract

620 Background: For patients (pts) with node-positive BC, TAC confers signficant disease-free and overall survival benefits vs FAC (5-fluorouracil, doxorubicin, cyclophosphamide), but with a higher rate of febrile neutropenia (Martin, SABCS 2003 ab 43). In our study of TAC vs FAC for node-negative BC, we performed an interim safety analysis to assess the impact of GF support on the incidence of TAC-related adverse events. Methods: Following surgery, patients (pts) with operable, high-risk (St Gallen, 1998), node-negative BC, 18–70 yr old, KPS ≥ 80%, and adequate hematologic and organ function were randomized to FAC (F 500 mg/m2, A 50 mg/m2, C 500 mg/m2) or TAC (T 75 mg/m2, A 50 mg/m2, C 500 mg/m2) day 1 every 3 wk for 6 cycles. After enrollment of 224 pts, the study was amended to require prophylactic G-CSF for pts subsequently treated with TAC, but not FAC. The present analysis assessed the impact of G-CSF on the incidence of febrile neutropenia (FN; fever ≥ grade 2 with gr 4 neutropenia) and other gr 3/4 toxicities in pts treated with TAC. Results: At the cut-off date for this analysis, 448 pts had been enrolled: 124 received FAC (111 prior to amendment) and 124 TAC (109 without mandatory G-CSF [TAC-G]; 115 with G-CSF [TAC+G]). For pts receiving FAC, the incidence of FN (% pts) was 1.3% (0.9% pre-, 1.7% post-amendment); other gr 3/4 adverse events were observed in 26.7% (27% pre-, 26.5% post-amendment). Among pts treated with TAC, the rates of FN were 23.8% for TAC-G (95% CI: 15.9–31.9%) and 3.5% for TAC+G (1.0–8.7%); the rates of other gr 3/4 toxicities were 50.4% for TAC-G (41.1–59.8%) and 20% for TAC+G (12.7–27.3%). The relative dose intensities for TAC-G vs TAC+G, respectively, were T: 92% vs 96%, A: 93% vs 97%, C: 93% vs 97%. Conclusion: Within the limitations of a non-randomized comparison, the use of G-CSF beginning with the first cycle of TAC substantially reduces the incidence of FN and other gr 3/4 toxicities and enables maintenance of chemotherapy dose intensity for women with early stage breast cancer. The adverse event rate with TAC+G is similar to that of FAC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis