Phase III Randomized Trial of Dose Intensive Neoadjuvant Chemotherapy with or Without G‐CSF in Locally Advanced Breast Cancer: Long‐Term Results

Learning Objectives After completing this course, the reader will be able to: Compare outcomes in patients treated with standard fluorouracil, doxorubicin, and cyclophosphamide (FAC) and those treated with dose‐intense FAC. Describe toxicity profiles in patients treated with standard fluorouracil, doxorubicin, and cyclophosphamide (FAC) and those treated with dose‐intense FAC. This article is available for continuing medical education credit at CME.TheOncologist.com Objective. To compare the pathologic complete response (pCR) rate of patients treated with 5‐fluorouracil (5‐FU), doxorubicin, and cyclophosphamide (FAC) versus dose‐intense FAC plus G‐CSF in the neoadjuvant setting and to compare the delivered dose intensity, disease‐free survival (DFS) and overall survival (OS) times, and toxicity between treatment arms in patients with breast cancer. Methods. Patients were randomized to receive preoperative FAC (5‐FU, 500 mg/m2; doxorubicin, 50 mg/m2; cyclophosphamide, 500 mg/m2) every 21 days for four cycles or dose‐intense FAC (5‐FU, 600 mg/m2; doxorubicin, 60 mg/m2; cyclophosphamide, 1,000 mg/m2) plus G‐CSF every 18 days for four cycles. Results. Two hundred two patients were randomly assigned. The median follow‐up was 7.5 years. Patients randomized to FAC plus G‐CSF had a higher pCR rate as well as clinical complete response rate; however, these differences were not statistically different from those with the FAC arm. Patients in the FAC + G‐CSF arm had a higher delivered dose intensity of doxorubicin in the neoadjuvant and adjuvant settings than those in the standard FAC arm. DFS and OS times were not significantly different between the two groups. However, the OS and DFS rates were significantly higher for patients who achieved a pCR than for those who did not. Thrombocytopenia, febrile neutropenia, and infection rates were higher in the FAC + G‐CSF arm. Conclusions. A higher delivered dose intensity of doxorubicin with the FAC + G‐CSF regimen did not result in a statistically significant higher pCR rate. However, patients who achieved a pCR experienced longer DFS and OS times. 摘要 目的 ：比较新辅助化疗应用5‐氟尿嘧啶（5‐FU）、多柔比星和环磷酰胺的FAC方案与大剂量FAC联合粒细胞集落刺激因子（G‐CSF）方案治疗乳腺癌患者的病理完全缓解率（pCR），同时比较两个乳腺癌治疗组的剂量强度（DI）、无病生存期（DFS）、总生存期（OS）和毒性反应。 方法 ：患者于术前随机接受FAC方案（5‐FU 500 mg/m2；多柔比星50 mg/m2；环磷酰胺500 mg/m2）× 4周期，每21天重复，或大剂量FAC（5‐FU 600 mg/m2；多柔比星60 mg/m2；环磷酰胺1,000 mg/m2）+ G‐CSF方案× 4周期，每18天重复。 结果. 共随机了202例患者。中位随访时间为7.5年。随机至FAC + G‐CSF治疗的患者pCR和临床完全缓解（CR）率较高，但是与FAC组相比差异未达到统计学显著意义。在新辅助化疗