TITAN：多柔比星/环磷酰胺序贯伊沙匹隆或紫杉醇用于早期三阴性乳腺癌的III期研究。
TITAN: phase III study of doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early-stage triple-negative breast cancer.
作者信息
Yardley Denise A, Arrowsmith Edward R, Daniel Brooke R, Eakle Janice, Brufsky Adam, Drosick David R, Kudrik Fred, Bosserman Linda D, Keaton Mark R, Goble Sharon A, Bubis Jeffrey A, Priego Victor M, Pendergrass Kelly, Manalo Yvonne, Bury Martin, Gravenor Donald S, Rodriguez Gladys I, Inhorn Roger C, Young Robyn R, Harwin William N, Silver Caryn, Hainsworth John D, Burris Howard A
机构信息
Sarah Cannon Research Institute, 250 25th Avenue North, Suite 100, Nashville, TN, 37203, USA.
Tennessee Oncology, Nashville, TN, USA.
出版信息
Breast Cancer Res Treat. 2017 Aug;164(3):649-658. doi: 10.1007/s10549-017-4285-6. Epub 2017 May 15.
PURPOSE
Ixabepilone is a microtubule stabilizer with activity in taxane-refractory metastatic breast cancer and low susceptibility to taxane-resistance mechanisms including multidrug-resistant phenotypes and high β-III tubulin expression. Since these resistance mechanisms are common in triple-negative breast cancer (TNBC), ixabepilone may have particular advantages in this patient population. This study evaluated the substitution of ixabepilone for paclitaxel following doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of early-stage TNBC.
METHODS
Patients with operable TNBC were eligible following definitive breast surgery. Patients were randomized (1:1) to receive four cycles of AC followed by either four cycles (12 weeks) of ixabepilone or 12 weekly doses of paclitaxel.
RESULTS
614 patients were randomized: 306 to AC/ixabepilone and 308 to AC/paclitaxel. At a median follow-up of 48 months, 59 patients had relapsed (AC/ixabepilone, 29; AC/paclitaxel, 30). The median time from diagnosis to relapse was 20.8 months. The 5-year disease-free survival (DFS) rates of the two groups were similar [HR 0.92; ixabepilone 87.1% (95% CI 82.6-90.5) vs. paclitaxel 84.7% (95% CI 79.7-88.6)]. The estimated 5-year overall survival (OS) rates were also similar [HR 1.1; ixabepilone 89.7% (95% CI 85.5-92.7) vs. paclitaxel 89.6% (95% CI 85.0-92.9)]. Peripheral neuropathy was the most common grade 3/4 event. Dose reductions and treatment discontinuations occurred more frequently during paclitaxel treatment.
CONCLUSIONS
Treatment with AC/ixabepilone provided similar DFS and OS in patients with operable TNBC when compared to treatment with AC/paclitaxel. The two regimens had similar toxicity, although treatment discontinuation, dose modifications, and overall peripheral neuropathy were more frequent with AC/paclitaxel.
TRIAL REGISTRATION
Clinical Trials.gov Identifier, NCT00789581.
目的
伊沙匹隆是一种微管稳定剂，对紫杉烷难治性转移性乳腺癌具有活性，且对包括多药耐药表型和高β-III微管蛋白表达在内的紫杉烷耐药机制敏感性较低。由于这些耐药机制在三阴性乳腺癌（TNBC）中很常见，伊沙匹隆在该患者群体中可能具有特殊优势。本研究评估了在早期TNBC的辅助治疗中，用伊沙匹隆替代多柔比星/环磷酰胺（AC）方案后使用的紫杉醇。
方法
可手术TNBC患者在确定性乳房手术后符合入选标准。患者被随机分组（1:1），接受四个周期的AC治疗，随后接受四个周期（12周）的伊沙匹隆治疗或每周一次共12剂的紫杉醇治疗。
结果
614例患者被随机分组：306例接受AC/伊沙匹隆治疗，308例接受AC/紫杉醇治疗。在中位随访48个月时，59例患者复发（AC/伊沙匹隆组29例；AC/紫杉醇组30例）。从诊断到复发的中位时间为20.8个月。两组的5年无病生存率（DFS）相似[风险比（HR）0.92；伊沙匹隆组为87.1%（95%置信区间82.6 - 90.5），紫杉醇组为84.7%（95%置信区间79.7 - 88.6）]。估计的5年总生存率（OS）也相似[HR 1.1；伊沙匹隆组为89.7%（95%置信区间85.5 - 92.7），紫杉醇组为89.6%（95%置信区间85.0 - 92.9）]。周围神经病变是最常见的3/4级事件。在紫杉醇治疗期间，剂量减少和治疗中断更为频繁。
结论
与AC/紫杉醇治疗相比，AC/伊沙匹隆治疗在可手术TNBC患者中提供了相似的DFS和OS。两种方案的毒性相似，尽管AC/紫杉醇治疗导致治疗中断、剂量调整和总体周围神经病变更为频繁。
试验注册
ClinicalTrials.gov标识符，NCT00789581。
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