title: Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial.
abstract: BACKGROUND
  As novel treatments carry substantial price tags and are mostly cost-prohibitive in low- and middle-income countries, there is an urgent need to develop alternatives, such as off-patent drugs. Megestrol acetate (MA) has a longstanding history in the treatment of breast cancer, but recently it is being used less often due to the advent of newer agents.
  
  
  METHODS
  This two-stage phase II trial evaluated the antitumor activity and toxicity of MA in postmenopausal women with hormone-sensitive advanced breast cancer who had experienced disease progression on a third-generation nonsteroidal aromatase inhibitor (NSAI). Eligible patients had metastatic breast cancer treated with a NSAI with at least 6-month progression-free survival (PFS), or relapse after ≥1 year on adjuvant NSAI. Patients received MA at a single daily oral dose of 160 mg. Primary end point was clinical benefit rate (CBR).
  
  
  RESULTS
  Forty-eight patients were enrolled. The CBR was 40% [95% confidence interval (CI) 25% to 55%], and the median duration of clinical benefit was 10.0 (95% CI 8.0-14.2) months. The median PFS was 3.9 (95% CI 3.0-4.8) months. The most common grade 3 adverse events were anemia (2%), dyspnea (2%), fatigue (2%), musculoskeletal pain (4%), deep vein thrombosis (10%), and weight gain (2%).
  
  
  CONCLUSIONS
  This is the first study to prospectively evaluate the efficacy and safety of MA in postmenopausal women with hormone-sensitive disease progressing on a NSAI. MA has demonstrated activity and acceptable tolerability in this setting, and therefore remains a reasonable treatment option in a cost-sensitive environment. These results also provide the background for further evaluation of progestins in the treatment of breast cancer.
  
  
  RESULTS
  local trial number, related to the approval by the IRB: CEP 108/06.
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Electronic address: jose_bines@yahoo.com.
authors.forename: J
authors.initials: J
authors.lastname: Bines
authors.affiliation: Fred Hutchinson Cancer Research Center, Sage Bionetworks, Seattle, USA.
authors.forename: R
authors.initials: R
authors.lastname: Dienstmann
authors.affiliation: Department of Clinical Research, Instituto Nacional de Câncer, Rio de Janeiro.
authors.forename: R M
authors.initials: RM
authors.lastname: Obadia
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: L G P
authors.initials: LGP
authors.lastname: Branco
authors.affiliation: Department of Clinical Research, Instituto Nacional de Câncer, Rio de Janeiro.
authors.forename: D C
authors.initials: DC
authors.lastname: Quintella
authors.affiliation: Department of Clinical Research, Instituto Nacional de Câncer, Rio de Janeiro.
authors.forename: T M
authors.initials: TM
authors.lastname: Castro
authors.affiliation: Neonathology Unit, Hospital Federal de Bonsucesso, Rio de Janeiro.
authors.forename: P G
authors.initials: PG
authors.lastname: Camacho
authors.affiliation: Department of Anatomic Pathology, A.C. Camargo Cancer Center, São Paulo; Faculty of Dentistry, University of São Paulo, São Paulo.
authors.forename: F A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Radiology, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: M E F
authors.initials: MEF
authors.lastname: Costa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D019290:Megestrol Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D017698:Postmenopause
chemical_list: D047072:Aromatase Inhibitors; D019290:Megestrol Acetate
keywords: breast neoplasm; drug therapy; megestrol acetate