Hutcheon Andrew W, Heys Steven D, Sarkar Tarun K
University of Aberdeen Hospital, Aberdeen, Scotland
Breast Cancer Res Treat. 2003;79 Suppl 1:S19-24. doi: 10.1023/a:1024333725148.
Neoadjuvant chemotherapy produces substantial increases in clinical response rates and rates of breast conserving therapy. Pathologic response rate, though generally low, is an important outcome as it is presumably associated with eradication of micrometastatic disease and may likely result in improved outcomes. Anthracyclines have long been considered the most efficacious chemotherapy agents for neoadjuvant therapy of early breast cancer. Unfortunately, not all patients respond to neoadjuvant anthracycline-based chemotherapy. In an effort to improve primary tumor response, docetaxel, an active agent in breast cancer, has been evaluated in the neoadjuvant setting. Several randomized trials, including the NSABP B-27, GEPAR-duo, and the Aberdeen trial, evaluating docetaxel in sequence with a doxorubicin-based neoadjuvant regimen have been reported, with encouraging findings. We designed the Aberdeen trial with two primary aims: (1) to evaluate primary docetaxel in patients that initially fail a neoadjuvant anthracycline-based polychemotherapy regimen, and (2) to compare a docetaxel-based neoadjuvant regimen with a standard anthracycline-based regimen in patients who do respond to the first four cycles of the anthracycline-based regimen. Eligible patients (n = 162) had previously untreated large (> or = 3 cm) or locally advanced (T3, T4, T x N2) breast cancer. All received four cycles of CVAP, after which clinical response was assessed. Responding patients were then randomized to four additional cycles of CVAP or to docetaxel 100 mg/m2 every 3 weeks for four cycles. Patients failing to respond to CVAP received the docetaxel regimen. After the first four cycles of CVAP, the overall response rate (ORR) was 67%. Ultimately, responses were higher in the group randomized to docetaxel compared with those continuing CVAP (cCR: 94% vs. 66%; p = 0.001; pCR 34% vs. 16%; p = 0.04). The addition of docetaxel improved overall survival and disease-free survival for patients responding to four cycles of CVAP as compared with those receiving eight cycles of CVAP. Relative dose intensity was higher and the incidence of severe leukopenia was lower in the group randomized to docetaxel. These data and data from the NSABP B-27 and GEPAR-duo trials strongly support a combined anthracycline/docetaxel regimen in the neoadjuvant setting.
新辅助化疗可显著提高临床缓解率和保乳治疗率。病理缓解率虽然通常较低，但却是一项重要的结果，因为它可能与微转移病灶的清除相关，并且可能会带来更好的治疗结局。长期以来，蒽环类药物一直被认为是早期乳腺癌新辅助治疗中最有效的化疗药物。不幸的是，并非所有患者对基于蒽环类药物的新辅助化疗都有反应。为了提高原发肿瘤的缓解率，多西他赛这种乳腺癌治疗中的活性药物已在新辅助治疗环境中进行了评估。包括NSABP B - 27、GEPAR - duo和阿伯丁试验在内的多项随机试验报告了多西他赛与基于阿霉素的新辅助方案序贯使用的情况，结果令人鼓舞。我们设计阿伯丁试验有两个主要目的：（1）评估在最初对基于蒽环类药物的多药化疗方案治疗失败的患者中使用初始多西他赛的效果，以及（2）在对基于蒽环类药物方案的前四个周期有反应的患者中，比较基于多西他赛的新辅助方案与标准基于蒽环类药物的方案。符合条件的患者（n = 162）之前未接受过治疗，患有大型（≥3 cm）或局部晚期（T3、T4、TxN2）乳腺癌。所有患者均接受四个周期的CVAP治疗，之后评估临床反应。有反应的患者随后被随机分为接受另外四个周期的CVAP或每3周接受100 mg/m²多西他赛治疗四个周期。对CVAP无反应的患者接受多西他赛方案。在CVAP的前四个周期后，总体缓解率（ORR）为67%。最终，随机接受多西他赛治疗的组的缓解情况优于继续接受CVAP治疗的组（完全临床缓解：94%对66%；p = 0.001；病理完全缓解34%对16%；p = 0.04）。与接受八个周期CVAP治疗的患者相比，添加多西他赛改善了对四个周期CVAP有反应的患者的总生存期和无病生存期。随机接受多西他赛治疗的组的相对剂量强度更高，严重白细胞减少的发生率更低。这些数据以及NSABP B - 27和GEPAR - duo试验的数据有力地支持了在新辅助治疗中使用蒽环类药物/多西他赛联合方案。
