title: Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer.
abstract: BACKGROUND
  The objective of this study was to evaluate 3 different doses of (7α)-21-(4-[(diethylamino)methyl]-2 methoxyphenoxy)-7 methyl-19 norpregna-1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (TAS-108) in patients with recurrent, hormone-responsive breast cancer.
  
  
  METHODS
  In this randomized, double-blind, multicenter study, TAS-108 was administered daily at a dose of 40 mg, 80 mg, or 120 mg to postmenopausal patients with locally advanced, or inoperable, or metastatic hormone-receptor positive breast cancer. The primary efficacy outcome was clinical benefit (CB), defined as the total number of patients who achieved a complete response, a partial response, or stable disease for ≥24 weeks. The study was a 2-stage design in which 19 patients per dose group were planned in the first stage. If at least 3 patients in any dose group achieved a CB, then that dose group was to be allowed to continue enrolling for the second stage, and the group could include up to a total of 60 patients.
  
  
  RESULTS
  The 40-mg and 80-mg groups met the criterion and enrolled patients into the second stage. In the 40-mg group, there were 13 CB events in 60 patients (21.7%); and, in the 80-mg group, there were 12 CB events in 60 patients (20%). The 120-mg daily dose was stopped early, because it failed to achieve the criterion. For the 40-mg and 80-mg groups, the median time to progression was 15.0 weeks and 15.9 weeks, respectively. Only 1 drug-related serious adverse event (grade 3 hyperglycemia) was reported.
  
  
  CONCLUSIONS
  TAS-108 at 40 mg and 80 mg daily demonstrated clinical activity with an encouraging duration of benefit. Because of its superior safety profile, TAS-108 40 mg daily is recommended for further development.
authors: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. abuzdar@mdanderson.org
authors: Aman
authors: A
authors: Buzdar
authors: Charles
authors: C
authors: Vogel
authors: Lee
authors: L
authors: Schwartzberg
authors: August
authors: A
authors: Garin
authors: Alejandra
authors: A
authors: Perez
authors: James
authors: J
authors: Ingle
authors: Michele
authors: M
authors: Houghton
authors: Christopher
authors: C
authors: Zergebel
authors: Bill
authors: B
authors: Kimball
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D017698:Postmenopause
chemical_list: D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; C482068:TS 108; D004958:Estradiol