title: Phase II trial of utidelone as monotherapy or in combination with capecitabine in heavily pretreated metastatic breast cancer patients.
abstract: 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.
authors: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17# Panjiayuan Nanli, Beijing, 100021, China.
authors: Pin
authors: P
authors: Zhang
authors: Cancer Hospital, Tianjin Medical University, Tianjin, China.
authors: Zhongsheng
authors: Z
authors: Tong
authors: Shanxi Cancer Hospital, Taiyuan, Shanxi, China.
authors: Fuguo
authors: F
authors: Tian
authors: Shandong Cancer Hospital, Jinan, Shandong, China.
authors: Yongsheng
authors: Y
authors: Wang
authors: PLA General Hospital, Beijing, China.
authors: Junlan
authors: J
authors: Yang
authors: Tianjin People's Hospital, Tianjin, China.
authors: Weilian
authors: W
authors: Li
authors: Cancer Hospital, Peking University, Beijing, China.
authors: Lijun
authors: L
authors: Di
authors: Hebei Cancer Hospital, Shijiazhuang, Hebei, China.
authors: Wei
authors: W
authors: Liu
authors: Beijing Biostar Technologies, Ltd., Beijing, China.
authors: Li
authors: L
authors: Tang
authors: Beijing Biostar Technologies, Ltd., Beijing, China.
authors: Rongguo
authors: R
authors: Qiu
authors: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17# Panjiayuan Nanli, Beijing, 100021, China. xubh2014@126.com.
authors: Binghe
authors: B
authors: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000494:pharmacology / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D034261:Epothilones; D043823:Taxoids; D000069287:Capecitabine
keywords: Drug resistance; Metastatic breast cancer; Phase II trial; Utidelone