Nabholtz J M, Mackey J, Smylie M, Tonkin K
Northern Alberta Breast Cancer Program, Cross Cancer Institute, Edmonton, Canada.
Semin Oncol. 1998 Oct;25(5 Suppl 12):27-31.
Considering the recommended dose of the docetaxel/doxorubicin combination (75 mg/m2 and 50 mg/m2, respectively), we decided to proceed with a pilot program in untreated metastatic breast cancer aimed at defining a multidrug regimen that could be later randomly compared with a standard doxorubicin-containing polychemotherapy regimen with equidoses of doxorubicin such as the FAC protocol (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) in first-line metastatic and adjuvant treatment of breast cancer patients. We proceeded with a pilot phase II study of the TAC combination, which consists of docetaxel 75 mg/m2 as a 1-hour infusion preceded by doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2, both given as an intravenous bolus. Three hundred seventy courses were delivered in 54 anthracycline-naive patients, among whom 62% had visceral metastases. Median relative dose intensity was above 98% for all drugs. Grade 4 neutropenia was the main toxicity (70% of cycles) and the incidence of febrile neutropenia and infection was acceptable (6% and 0.8% of cycles, respectively). Acute and chronic extrahematologic toxicities were mild, mostly grade 2, and the docetaxel-specific toxicities (fluid retention, nail changes, etc) were not major clinical problems; no patient was discontinued due to fluid retention. The major response rate was 73% overall and 79% in measurable disease. Time to progression and survival are still under evaluation. The TAC combination is an active and well-tolerated regimen that is the basis of two currently open, pivotal, randomized phase III trials comparing TAC with FAC in the metastatic and adjuvant treatment of breast cancer.
考虑到多西他赛/阿霉素联合用药的推荐剂量（分别为75mg/m²和50mg/m²），我们决定在未经治疗的转移性乳腺癌患者中开展一项试点项目，旨在确定一种多药联合方案，随后可将其与含等量阿霉素的标准多药化疗方案（如FAC方案，5-氟尿嘧啶500mg/m²、阿霉素50mg/m²和环磷酰胺500mg/m²）进行随机对照，用于乳腺癌患者的一线转移性和辅助治疗。我们开展了一项TAC联合方案的II期试点研究，该方案包括先静脉推注阿霉素50mg/m²和环磷酰胺500mg/m²，然后静脉滴注多西他赛75mg/m²，持续1小时。在54例未接受过蒽环类药物治疗的患者中进行了370个疗程的治疗，其中62%的患者有内脏转移。所有药物的中位相对剂量强度均高于98%。4级中性粒细胞减少是主要毒性反应（70%的疗程），发热性中性粒细胞减少和感染的发生率可以接受（分别为6%和0.8%的疗程）。急慢性血液学外毒性反应较轻，大多为2级，多西他赛特异性毒性反应（液体潴留、指甲改变等）并非主要临床问题；没有患者因液体潴留而停药。总体主要缓解率为73%，可测量病灶的缓解率为79%。疾病进展时间和生存期仍在评估中。TAC联合方案是一种有效的、耐受性良好的方案，是目前两项正在进行的、关键的、随机III期试验的基础，这两项试验在乳腺癌的转移性和辅助治疗中将TAC与FAC进行比较。
