Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early Stage Breast Cancer and Evaluation of βIII‐Tubulin Expression as a Predictive Marker. (12th July 2013)

• Record Type: Journal Article
• Authors: Saura, Cristina; Tseng, Ling‐Ming; Chan, Stephen; Chacko, Raju T.; Campone, Mario; Manikhas, Alexy; Nag, Shona M.; Leichman, Cynthia G.; Dasappa, Lokanatha; Fasching, Peter A.; Hurtado de Mendoza, Fernando; Symmans, W. Fraser; Liu, David; Mukhopadhyay, Pralay; Horak, Christine; Xing, Guan; Pusztai, Lajos
• Is Part Of: Oncologist. Volume 18:Number 7(2013)
• Page Start: 787
• Page End: 794
• Publication Date: 2013-07-12
• Subjects: Ixabepilone -- Neoadjuvant -- Biomarker -- βIII‐Tubulin -- Early stage breast cancer; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2013-0075
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : Background: This randomized phase II trial was designed to compare the rate of pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage breast cancer (BC). Expression of βIII‐tubulin as a predictive marker was also evaluated. Patients and Methods: Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received four cycles of AC followed by 1:1 randomization to either ixabepilone 40 mg/m 2 (3‐hour infusion) every 3 weeks for four cycles ( n = 148) or weekly paclitaxel 80 mg/m 2 (1‐hour infusion) for 12 weeks ( n = 147). All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis prior to chemotherapy. βIII‐Tubulin expression was assessed using immunohistochemistry. Results: There was no significant difference in the rate of pCR in the ixabepilone treatment arm (24.3%; 90% confidence interval [CI], 18.6–30.8) and the paclitaxel treatment arm (25.2%; 90% CI, 19.4–31.7). βIII‐Tubulin‐positive patients obtained higher pCR rates compared with βIII‐tubulin‐negative patients in both treatment arms; however, βIII‐tubulin expression was not significantly associated with a differential response to ixabepilone or paclitaxel. The safety profiles of both regimens were generally similar, although neutropenia occurred more frequently in the ixabepilone arm (grade 3/4: 41.3% vs. 8.4%). The most common nonhematologic toxicity was peripheral neuropathy. Conclusions: Neoadjuvant treatment of early stage BC with AC followed by ixabepilone every 3 weeks or weekly paclitaxel was well tolerated with no significant difference in efficacy. Higher response rates were observed among βIII‐tubulin‐positive patients. Abstract : This randomized phase II trial compared the rate of pathologic complete response induced by neoadjuvant cyclophosphamide plus doxorubicin followed by ixabepilone or paclitaxel in women with early stage breast cancer. Expression of βIII‐tubulin as a predictive marker was also evaluated. Neoadjuvant treatment was well tolerated, with no significant difference in efficacy, and higher response rates were observed among βIII‐tubulin‐positive patients. Abstract : 摘要 背景 . 本项随机II期临床试验旨在对早期乳腺癌（BC）女性患者使用环磷酰胺联合阿霉素（AC）序贯 伊沙匹隆或紫杉醇的新辅助治疗诱导的病理完全缓解（pCR）率进行比较。亦对βIII微管蛋白表达作为预测标记的价值进行了评价。 对象和方法 . 既往未经治疗、经组织学证实为原发性浸润性乳腺腺癌的女性患者接受AC方案4个疗程后，以1:1的比例随机接受伊沙匹隆（40 mg/m 2 ，静脉滴注3小时，每3周一次，共计4个疗程， n = 148）或紫杉醇（80 mg/m 2 ，静脉滴注1小时，每周一次，共计12周， n =147）序贯治疗。所有患者在化疗前接受原发癌的芯针活组织检查以作分子标记分析。使用免疫组化方法评估βIII微管蛋白的表达情况。 结果 . 伊沙匹隆治疗组[24.3%；90%可信区间（CI），18.6% ~ 30.8%]和紫杉醇治疗组（25.2%；90% CI，19.4% ~31.7%）患者的pCR率差异无统计学意义。在两个治疗组中，βIII微管蛋白阳性患者获得的pCR率均高于βIII微管蛋白阴性患者，但βIII微管蛋白的表达与患者对伊沙匹隆或紫杉醇的治疗应答差异无显著相关性。两种方案的安全谱基本相似，但伊沙匹隆组患者中性粒细胞减少症的发生率更高（3/4级：41.3% vs. 8.4%）。最常见的非血液系统毒性反应为周围神经病变。 结论 . 早期BC患者对AC序贯每3周一次的伊沙匹隆或每周一次的紫杉醇新辅助治疗均具有良好的耐受性，且在疗效方面无显著差异。研究观察到βIII微管蛋白阳性患者的缓解率更高。