Zhang Pin, Tong Zhongsheng, Tian Fuguo, Wang Yongsheng, Yang Junlan, Li Weilian, Di Lijun, Liu Wei, Tang Li, Qiu Rongguo, Xu Binghe
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17# Panjiayuan Nanli, Beijing, 100021, China.
Cancer Hospital, Tianjin Medical University, Tianjin, China.
J Hematol Oncol. 2016 Aug 11;9(1):68. doi: 10.1186/s13045-016-0297-7.
The treatment of metastatic breast cancer (MBC) remains a great clinical challenge as drug resistance frequently develops. Alternative agents that can overcome drug resistance would offer new therapeutic options. The primary aim of this phase II study was to evaluate the efficacy and safety of utidelone as a monotherapy or in combination with capecitabine in metastatic breast cancer patients previously treated with and resistant to anthracyclines and taxanes.
In two open-label, noncomparative clinical studies, patients with metastatic breast cancer who previously received anthracycline- and/or taxane-containing regimens were given (1) 25 to 35 mg/m(2)/day intravenously infused utidelone, once daily for 5 days, in combination with 14 days of 2000 mg/m(2) capecitabine, divided in two equal daily oral doses or (2) 40 mg/m(2)/day intravenously infused utidelone, once daily for 5 days. These regimens were administered per each 21-day treatment cycle, and the maximum of treatment cycles allowed per protocol is 6. Objective response rate (ORR), progression-free survival (PFS), and tolerability were evaluated.
In the combination study, 33 patients completed a median of 6 cycles of therapy, which was the highest cycles a trial patient could receive under the criteria of the study protocol. Efficacy was evaluated (n = 32) with an ORR of 42.4 % (FAS, 95 % CI, 26.6, 60.9) and a median PFS of 7.9 (FAS, 95 % CI, 6.1, 9.8) months. The monotherapy study (n = 63) resulted in an ORR of 28.57 % (FAS, 95 % CI, 18.4, 40.6) and a median PFS of 5.4 (FAS, 95 % CI, 2.9, 9.8) months. In both studies, common toxicities associated with utidelone administration included peripheral neuropathy, fatigue, myalgia, and arthralgia, but the toxicities were limited and manageable. Notably, very mild myelosuppression, low liver and renal toxicities, and very limited gastrointestinal toxic effect were observed, in contrast to other agents in the same class.
Utidelone showed promising efficacy, tolerability, and advantageous safety profiles in the treatment of patients with advanced anthracycline/taxane-refractory metastatic breast cancer and may offer new treatment options to overcome drug resistance.
CHiCTR-TRC-13004205 , registered on August 15, 2013.
转移性乳腺癌（MBC）的治疗仍然是一项巨大的临床挑战，因为耐药性经常出现。能够克服耐药性的替代药物将提供新的治疗选择。这项II期研究的主要目的是评估乌替德洛作为单一疗法或与卡培他滨联合用于先前接受过蒽环类药物和紫杉烷治疗且耐药的转移性乳腺癌患者的疗效和安全性。
在两项开放标签、非对照的临床研究中，先前接受含蒽环类药物和/或紫杉烷方案治疗的转移性乳腺癌患者被给予：（1）静脉输注乌替德洛25至35mg/m²/天，每日一次，共5天，联合卡培他滨2000mg/m²，共14天，分两次等量口服，或（2）静脉输注乌替德洛40mg/m²/天，每日一次，共5天。这些方案每21天治疗周期给药一次，根据方案允许的最大治疗周期为6个。评估客观缓解率（ORR）、无进展生存期（PFS）和耐受性。
在联合治疗研究中,33例患者完成了中位6个周期的治疗，这是根据研究方案标准试验患者能够接受的最高周期数。对疗效进行了评估（n = 32），ORR为42.4%（全分析集，95%CI，26.6，60.9）,中位PFS为7.9个月（全分析集，95%CI，6.1，9.8）。单一疗法研究（n = 63）的ORR为28.57%（全分析集，95%CI，18.4，40.6），中位PFS为5.4个月（全分析集，95%CI，2.9，9.8）。在两项研究中，与乌替德洛给药相关的常见毒性包括周围神经病变、疲劳、肌痛和关节痛，但毒性有限且可控。值得注意的是，与同一类别的其他药物相比，观察到非常轻微的骨髓抑制、低肝毒性和肾毒性以及非常有限的胃肠道毒性作用。
乌替德洛在治疗晚期蒽环类/紫杉烷难治性转移性乳腺癌患者中显示出有前景的疗效、耐受性和有利的安全性，可能为克服耐药性提供新的治疗选择。
CHiCTR - TRC - 13004205，于2013年8月15日注册。
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