Bandos Hanna, Melnikow Joy, Rivera Donna R, Swain Sandra M, Sturtz Keren, Fehrenbacher Louis, Wade James L, Brufsky Adam M, Julian Thomas B, Margolese Richard G, McCarron Edward C, Ganz Patricia A
NRG Oncology and The University of Pittsburgh, Pittsburgh, PA; Center for Healthcare Policy and Research, University of California Davis, Sacramento, CA; Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD; NRG Oncology and The Washington Cancer Institute at Washington Hospital Center, Washington, DC and current: Georgetown University, Washington, DC; NRG Oncology and The Colorado Cancer Research Program, Denver, CO; NRG Oncology and Kaiser Permanente, Northern California, Vallejo, CA; NRG Oncology and The Central Illinois CCOP Heartland NCORP, Decatur, IL; NRG Oncology and The University of Pittsburgh/Magee Womens Hospital, Pittsburgh, PA; NRG Oncology and The Allegheny Health Network, Pittsburgh, PA; NRG Oncology and The Jewish General Hospital, McGill University, Montréal, QC, Canada; NRG Oncology and The MedStar Franklin Square Medical Center/Harry and Jeanette Weinberg Cancer Institute, Baltimore, MD; NRG Oncology and The University of California Los Angeles, Schools of Medicine and Public Health, Los Angeles, CA; Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA.
J Natl Cancer Inst. 2018 Feb 1;110(2). doi: 10.1093/jnci/djx162.
The long-term effects of chemotherapy are sparsely reported. Peripheral neuropathy (PN) is one of the most frequent toxicities associated with taxane use for the treatment of early-stage breast cancer. We investigated the impact of the three different docetaxel-based regimens and patient characteristics on long-term, patient-reported outcomes of PN and the impact of PN on long-term quality of life (QOL).
The National Surgical Adjuvant Breast and Bowel Project Protocol B-30 was a randomized trial comparing sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T) (AC→T), concurrent ACT, or AT in women with node-positive, early-stage breast cancer. The AC→T group had a higher cumulative dose of T. PN was one of the symptoms assessed in a QOL substudy. Statistical methods included simple and mixed ordinal logistic regression and general linear models. All statistical tests were two-sided.
Of 1512 patients, 41.9% reported PN two years after treatment initiation. Treatment with AT and ACT was associated with less severe long-term PN compared with AC→T (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.35 to 0.58; OR = 0.59, 95% CI = 0.46 to 0.75). Preexisting PN, older age, obesity, mastectomy, and greater number of positive nodes were also associated with higher risk of long-term PN. Patients who reported worse PN symptoms at 24 months had statistically significantly worse QOL (Ptrend < .001).
The administration of docetaxel is associated with long-term PN. The lower rate of long-term PN in AT and ACT patients might be an important consideration in supporting choosing these therapies for individuals with preexisting neuropathic symptoms or other risk factors for neuropathy.
化疗的长期影响鲜有报道。外周神经病变（PN）是与紫杉烷类药物用于治疗早期乳腺癌相关的最常见毒性反应之一。我们研究了三种不同的多西他赛方案及患者特征对患者报告的PN长期结局的影响，以及PN对长期生活质量（QOL）的影响。
国家外科辅助乳腺和肠道项目协议B-30是一项随机试验，比较了序贯使用阿霉素（A）和环磷酰胺（C）后使用多西他赛（T）（AC→T）、同步使用ACT或AT方案，用于治疗淋巴结阳性的早期乳腺癌女性患者。AC→T组的T累积剂量更高。PN是生活质量子研究中评估的症状之一。统计方法包括简单和混合有序逻辑回归以及一般线性模型。所有统计检验均为双侧检验。
在1512例患者中，41.9%在开始治疗两年后报告出现PN。与AC→T相比，AT和ACT治疗导致的长期PN严重程度较低（优势比[OR]=0.45，95%置信区间[CI]=0.35至0.58；OR = 0.59，95%CI = 0.46至0.75）。既往存在PN、年龄较大、肥胖、乳房切除术以及阳性淋巴结数量较多也与长期PN风险较高相关。在24个月时报告PN症状较差的患者，其生活质量在统计学上显著较差（Ptrend <.001）。
多西他赛的使用与长期PN相关。AT和ACT患者中较低的长期PN发生率可能是支持为有既往神经病变症状或其他神经病变风险因素的个体选择这些治疗方法的一个重要考虑因素。
