Dose-dense (DD) AC followed by paclitaxel is associated with moderate, frequent anemia compared to sequential (S) and/or less DD Treatment: Update by CALGB on Breast Cancer Intergroup Trial C9741 with ECOG, SWOG, & NCCTG

Abstract

620 Background: C9741 demonstrated superior DFS and OS for q14 day A, T, and C compared to q21 day treatment and no difference in outcomes with concurrent vs. sequential A and C. (J Clin Oncol 21:1431–39. 2003) Study design: Arm S3: Ax4 ->Tx4->Cx4 q3 weeks; Arm S2 (DD): Ax4->Tx4->Cx4 q2 weeks with filgrastim; Arm C3: ACx4->Tx4 q3 weeks; Arm C2 (DD): ACx4->Tx4 q2 weeks with filgrastim; A=doxorubicin 60mg/m2, T=paclitaxel 175 mg/m2 over 3 hours, and C=cyclophosphamide 600mg/m2. Red cell transfusion was observed in 13% of the first 412 patients (3,973 treatment cycles) with C2, compared to less than 4% in S2 and C3, and zero in S3. This observation prompted a more detailed review of the toxicity data. Methods: We performed a retrospective review of hemoglobin per course, use of epoetin alpha and transfusions. Use of epoetin alpha and transfusions were at discretion of physician. Time-to-event distributions were estimated by the Kaplan-Meier technique; two or more such distributions were compared with the logrank test. Chi-square tests compared two or more proportions; Results: Grade 2 anemia (hemoglobin < 10g/dL) was more frequent in C2, AC->T q 2 weeks. On treatment, 23% of C2 had ≥ Grade 2 anemia compared to 3% (S3), 11% (S-2) and 8% (C-3), P<0.0001. At cycle 5, C2 had the lowest nadir hemoglobin of 10.7 g/dL, 0.9 g/dL lower than the other arms. Epoetin alpha use was highest in C2 (11%) compared to S2 (5%), C3 (7%) and S3 (1%), with significantly greater epoetin alpha use at course 5, P=0.013. Conclusions: Dose-dense AC->T q14 days in C2 is associated with a greater incidence of moderate anemia, higher use of epoetin alpha and more red cell transfusions than the other arms. Red cell growth factors should be considered to reduce the severity of anemia. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, Genentech Amgen, Bristol-Myers Squibb, Genentech Amgen, Bristol-Myers Squibb, Bristol