title: Trabectedin as a single-agent treatment of advanced breast cancer after anthracycline and taxane treatment: a multicenter, randomized, phase II study comparing 2 administration regimens.
abstract: BACKGROUND
  The purpose of this study was to assess the efficacy and safety of trabectedin for advanced breast cancer.
  
  
  METHODS
  In an open-label, phase II, multicenter study, women with advanced breast cancer previously treated with ≤ 2 lines of chemotherapy for advanced disease, including both anthracyclines and taxanes, were randomized (1:1) to 3-hour infusions of trabectedin 1.3 mg/m(2) once every 3 weeks (1/3 treatment arm) or 0.58 mg/m(2) every week for 3 of 4 weeks (3/4 treatment arm). The primary end point was objective response. Secondary end points included time to progression (TTP), progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  Fifty-two women (median age, 50 years; median chemotherapy agents, 4) were enrolled. Relative trabectedin dose intensities were 81% and 76% in the 1/3 and 3/4 treatment arms, respectively. Objective response rates were 12% (3 of 25) and 4% (1 of 27), respectively. Stable disease was observed in 14 (56%) and 11 (41%) patients in the 1/3 and 3/4 treatment arms, respectively, with median durations of 3.5 and 3.7 months. Median TTP and PFS were higher in the 1/3 treatment arm (3.1 months each) than in the 3/4 treatment arm (2.0 months each). At a median follow-up of 7 months in both treatment arms, median OS was not reached in the 1/3 treatment arm and was 9.4 months in the 3/4 treatment arm. The most frequent drug-related adverse events in the 1/3 and 3/4 treatment arms, respectively, were alanine aminotransferase (ALT) level increases (68% vs. 63%), nausea (56% vs. 59%), and asthenia (56% vs. 48%). Neutropenia and increases in ALT levels were the most frequent grade 3/4 events. Both types of events were usually transient and reversible.
  
  
  CONCLUSIONS
  In the population studied, trabectedin showed a manageable safety profile for both regimens analyzed. There were higher objective response rates and a longer PFS in the 1/3 treatment arm compared with the 3/4 treatment arm.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA. Electronic address: Lori.Goldstein@fccc.edu.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Goldstein
authors.affiliation: Oncology/Hematology, East Jefferson General Hospital, Metaire, LA.
authors.forename: Jayne
authors.initials: J
authors.lastname: Gurtler
authors.affiliation: Hematology/Oncology PC, Stamford, CT.
authors.forename: Salvatore A
authors.initials: SA
authors.lastname: Del Prete
authors.affiliation: Cancer Research Center, Moscow, Russia.
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
authors.affiliation: NN Petrov Research Institute of Oncology, St Petersburg, Russia.
authors.forename: Vladimir F
authors.initials: VF
authors.lastname: Semiglazov
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ.
authors.forename: Eliel
authors.initials: E
authors.lastname: Bayever
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Michiels
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004149:Dioxoles / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage; D000077606:Trabectedin; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D004149:Dioxoles; D043823:Taxoids; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
keywords: Ecteinascidin-743; Objective response rate; Overall survival; Progression-free survival; Safety; Time to progression