Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Lancet Oncol. 2009 Dec;10(12):1145-51. doi: 10.1016/S1470-2045(09)70307-9. Epub 2009 Nov 10.
Standard adjuvant chemotherapy regimens for patients with moderate-to-high-risk early breast cancer typically contain a taxane, an anthracycline, and cyclophosphamide. We aimed to investigate whether integration of capecitabine into such a regimen enhances outcome.
In this open-label trial, we randomly assigned (centrally by computer; stratified by node status, HER2 status, and centre) 1500 women with axillary node-positive or high-risk node-negative breast cancer to either three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753), or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The primary endpoint was recurrence-free survival. A planned interim analysis was done after 3 years' median follow-up. Efficacy analyses were by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT00114816.
Two patients in each group were excluded from efficacy analyses because of withdrawal of consent or distant metastases. After a median follow-up of 35 months (IQR 25.5-43.6), recurrence-free survival at 3 years was better with the capecitabine regimen than with control (93%vs 89%; hazard ratio 0.66, 95% CI 0.47-0.94; p=0.020). The capecitabine regimen was associated with more cases of grade 3 or 4 diarrhoea (46/740 [6%] vs 25/741 [3%]) and hand-foot syndrome (83/741 [11%] vs 2/741 [<1%]) and the control regimen with more occurrences of grade 3 or 4 neutropenia (368/375 [98%] vs 325/378 [86%]) and febrile neutropenia (65/741 [9%] vs 33/742 [4%]). More patients discontinued planned treatment in the capecitabine group than in the control group (178/744 [24%] vs 23/741 [3%]). Four patients in the capecitabine group and two in the control group died from potentially treatment-related causes.
The capecitabine-containing chemotherapy regimen reduced breast cancer recurrence compared with a control schedule of standard agents. Capecitabine administration was frequently discontinued because of adverse effects.
Roche, Sanofi-Aventis, AstraZeneca, Cancer Society of Finland.
中高危早期乳腺癌患者的标准辅助化疗方案通常包含紫杉烷类、蒽环类和环磷酰胺。我们旨在研究卡培他滨与这种方案联合应用是否能提高疗效。
本开放标签试验采用中央计算机（按淋巴结状态、HER2 状态和中心分层）随机分配 1500 例腋窝淋巴结阳性或高危淋巴结阴性乳腺癌患者，分别接受卡培他滨和多西他赛（卡培他滨组，n=753）或多西他赛（对照组，n=747）治疗 3 个周期，然后再接受卡培他滨、表柔比星和环磷酰胺（卡培他滨组）或多西他赛、表柔比星和氟尿嘧啶（对照组）3 个周期。主要终点为无复发生存。中位随访 3 年后进行了计划的中期分析。疗效分析采用改良意向治疗。该研究在 ClinicalTrials.gov 注册，编号为 NCT00114816。
每组各有 2 例患者因退出同意或远处转移而被排除在疗效分析之外。中位随访 35 个月（IQR 25.5-43.6）后，卡培他滨组 3 年无复发生存率优于对照组（93%vs 89%；风险比 0.66，95%CI 0.47-0.94；p=0.020）。卡培他滨组更易发生 3 级或 4 级腹泻（46/740[6%]vs 25/741[3%]）和手足综合征（83/741[11%]vs 2/741[＜1%]），而对照组更易发生 3 级或 4 级中性粒细胞减少（368/375[98%]vs 325/378[86%]）和发热性中性粒细胞减少（65/741[9%]vs 33/742[4%]）。卡培他滨组比对照组更多患者停止计划治疗（178/744[24%]vs 23/741[3%]）。卡培他滨组 4 例患者和对照组 2 例患者死于可能与治疗相关的原因。
含卡培他滨的化疗方案与标准药物方案相比降低了乳腺癌复发率。由于不良反应，卡培他滨的给药经常被中断。
罗氏、赛诺菲-安万特、阿斯利康、芬兰癌症协会。
