III 期辅助试验比较三种化疗方案在可手术淋巴结阳性乳腺癌女性中的明确结果：NSABP B-38 试验。
Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial.
机构信息
Sandra M. Swain, Gong Tang, Charles E. Geyer Jr, Priya Rastogi, James N. Atkins, Paul P. Donnellan, Louis Fehrenbacher, Catherine A. Azar, André Robidoux, Jonathan A. Polikoff, Adam M. Brufsky, David D. Biggs, Edward A. Levine, John L. Zapas, Louise Provencher, Soonmyung Paik, Joseph P. Costantino, Eleftherios P. Mamounas, and Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project (NSABP); Norman Wolmark, Allegheny General Hospital, Allegheny Health Network; Gong Tang and Joseph P. Costantino, NSABP Biostatistical Center and University of Pittsburgh Graduate School of Public Health; Priya Rastogi, University of Pittsburgh Cancer Institute; Adam M. Brufsky, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Charles E. Geyer Jr, Virginia Commonwealth University, Richmond, VA; James N. Atkins, Southeast Cancer Control Consortium-Community Clinical Oncology Program, Goldsboro; Edward A. Levine, Wake Forest University, Winston-Salem, NC; Paul P. Donnellan, University Hospital, Galway, and the All-Ireland Cooperative Oncology Research Group, Dublin, Ireland; Louis Fehrenbacher, Kaiser Permanente Northern California, Vallejo; Jonathan A. Polikoff, Kaiser Permanente Southern California, San Diego, CA; Catherine A. Azar, Kaiser Permanente, Denver, CO; André Robidoux, Centre hopitalier de l'Université de Montréal (CHUM), Montréal; Louise Provencher, CHU de Québec, Hôpital du Saint-Sacrement, Québec City, QC, Canada; David D. Biggs, Helen F. Graham Cancer Center, Christiana Care Health System, Newark, DE; John L. Zapas, Medstar Franklin Square Medical Center, Baltimore, MD; Donald W. Northfelt, Mayo Clinic Arizona, Scottsdale, AZ; and Eleftherios P. Mamounas, MD Anderson Cancer Center, Orlando, FL.
出版信息
J Clin Oncol. 2013 Sep 10;31(26):3197-204. doi: 10.1200/JCO.2012.48.1275. Epub 2013 Aug 12.
PURPOSE
Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens.
PATIENTS AND METHODS
We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion.
RESULTS
There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95).
CONCLUSION
Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.
目的
蒽环类药物和紫杉烷类药物三药化疗方案已被证明对早期乳腺癌的辅助治疗有效。本试验（NSABP B-38；联合化疗治疗淋巴结阳性乳腺癌术后妇女）旨在探讨是否加入第四种药物可以提高疗效，并对两种标准方案进行直接比较。
患者和方法
我们将 4894 名淋巴结阳性早期乳腺癌患者随机分为六周期多西紫杉醇、多柔比星和环磷酰胺（TAC），四周期密集型（DD）多柔比星和环磷酰胺后四周期 DD 紫杉醇（P；DD AC→P），或 DD AC→P 加四周期吉西他滨（G）至 DD 紫杉醇（DD AC→PG）。需要进行初级粒细胞集落刺激因子支持；红细胞生成刺激剂（ESA）由研究者自行决定使用。
结果
DD AC→PG 和 DD AC→P 之间 5 年无病生存率（DFS）无显著差异（80.6%比 82.2%；HR，1.07；P =.41），DD AC→PG 和 TAC 之间 5 年总生存率（OS）无显著差异（80.6%比 80.1%；HR，0.93；P =.39），DD AC→PG 和 DD AC→P 之间 5 年 OS 无显著差异（90.8%比 89.1%；HR，0.85；P =.13），DD AC→PG 和 TAC 之间 5 年 OS 无显著差异（90.8%比 89.6%；HR，0.86；P =.17），DD AC→P 与 TAC 相比，DFS（HR，0.87；P =.07）和 OS（HR，1.01；P =.96）也无显著差异。TAC、DD AC→P 和 DD AC→PG 的 3 级至 4 级毒性分别为发热性中性粒细胞减少症（9%、3%、3%；P <.001）、感觉神经病变（< 1%、7%、6%；P <.001）和腹泻（7%、2%、2%；P <.001）。对于 ESA 的探索性分析显示，DFS 事件无相关性（HR，1.02；P =.95）。
结论
在 DD AC→P 中添加 G 并未改善结局。尽管毒性特征不同，但 DD AC→P 和 TAC 之间的疗效无显著差异。
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