剂量密集序贯辅助化疗，随后根据情况对早期乳腺癌患者给予曲妥珠单抗治疗一年：希腊合作肿瘤学组随机III期试验5年中位随访的首次报告
Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial.
作者信息
Fountzilas George, Dafni Urania, Papadimitriou Christos, Timotheadou Eleni, Gogas Helen, Eleftheraki Anastasia G, Xanthakis Ioannis, Christodoulou Christos, Koutras Angelos, Papandreou Christos N, Papakostas Pavlos, Miliaras Spyros, Markopoulos Christos, Dimitrakakis Constantine, Korantzopoulos Panagiotis, Karanikiotis Charisios, Bafaloukos Dimitrios, Kosmidis Paris, Samantas Epaminontas, Varthalitis Ioannis, Pavlidis Nicholas, Pectasides Dimitrios, Dimopoulos Meletios-Athanassios
机构信息
Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki Ring Road, 564 03 Thessaloniki, Macedonia, Greece.
出版信息
BMC Cancer. 2014 Jul 15;14:515. doi: 10.1186/1471-2407-14-515.
BACKGROUND
Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet.
METHODS
From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326). Trastuzumab was administered for one year to HER2-positive patients post-radiation.
RESULTS
At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) rate was 86%, 90% and 88%, for Arms A, B and C, respectively, while the 3-year overall survival (OS) rate was 96% in all arms. No differences were found in DFS or OS between the combined B and C Arms versus Arm A (DFS: HR = 0.81, 95% CI: 0.59-1.11, P = 0.20; OS: HR = 0.84, 95% CI: 0.55-1.30, P = 0.43). Among the 255 patients who received trastuzumab, 189 patients (74%) completed 1 year of treatment uneventfully. In all arms, the most frequently reported severe adverse events were neutropenia (30% vs. 27% vs. 26%) and leucopenia (12% vs. 13% vs. 12%), while febrile neutropenia occurred in fifty-one patients (6% vs. 4% vs. 5%). Patients in Arm A experienced more often severe pain (P = 0.002), neurological complications (P = 0.004) and allergic reactions (P = 0.004), while patients in Arm B suffered more often from severe skin reactions (P = 0.020).
CONCLUSIONS
No significant differences in survival between the regimens were found in the present phase III trial. Taxane scheduling influenced the type of severe toxicities. HER2-positive patients demonstrated comparable 3-year DFS and OS rates with those reported in other similar studies.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry ACTRN12610000151033.
背景
含蒽环类和紫杉烷类的剂量密集序贯化疗已用于高危可手术乳腺癌的辅助治疗。然而，剂量密集方案中更优的紫杉烷类药物及最佳给药方案尚未明确。
方法
2005年7月至2008年11月，1001例患者（990例符合条件）被随机分组，每2周接受1次治疗，A组（333例患者）：3个周期表柔比星110mg/m²，随后3个周期紫杉醇200mg/m²，接着3个周期强化CMF方案；B组（331例）：与A组一样，先接受3个周期表柔比星，再接受3个周期CMF方案，3周后接受9个周期多西他赛35mg/m²每周方案；C组（326例）：9个周期紫杉醇80mg/m²每周方案。HER2阳性患者放疗后给予曲妥珠单抗治疗1年。
结果
中位随访60.5个月时，A、B、C组3年无病生存率（DFS）分别为86%、90%和88%，3年总生存率（OS）在所有组均为96%。联合B组和C组与A组相比，DFS（风险比[HR]=0.81，95%置信区间[CI]：0.59 - 1.11，P = 0.20）和OS（HR = 0.84，95% CI：0.55 - 1.30，P = 0.43）均无差异。在接受曲妥珠单抗治疗的255例患者中，189例（74%）顺利完成1年治疗。所有组中，最常报告的严重不良事件为中性粒细胞减少（分别为30%、27%、26%）和白细胞减少（分别为12%、13%、12%），发热性中性粒细胞减少发生在51例患者中（分别为6%、4%、5%）。A组患者更常出现严重疼痛（P = 0.002）、神经并发症（P = 0.004）和过敏反应（P = 0.004），而B组患者更常出现严重皮肤反应（P = 0.020）。
结论
在本III期试验中，各方案间生存率无显著差异。紫杉烷类给药方案影响严重毒性类型。HER2阳性患者3年DFS和OS率与其他类似研究报告相当。
试验注册
澳大利亚和新西兰临床试验注册中心ACTRN12610000151033 。
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