title: Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  This multicenter phase II trial evaluated the efficacy and safety of trabectedin in metastatic castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  Two schedules were evaluated in three cohorts: weekly as 3-h i.v. infusion at 0.58 mg/m(2) for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m(2) (Cohort B1, n = 5) and 1.2 mg/m(2) (Cohort B2, n = 20). The primary end point was prostate-specific antigen (PSA) response; secondary end points included safety, tolerability and time to progression (TTP).
  
  
  RESULTS
  Trabectedin resulted in PSA declines ≥ 50% in 12.5% (Cohort A) and 10.5% (Cohort B2) of patients. Among men pretreated with taxane-based chemotherapy, PSA response was 13.6% (Cohort A) and 15.4% (Cohort B2). PSA responses lasted 4.1-8.6 months, and median TTP was 1.5 months (Cohort A) and 1.9 months (Cohort B2). The dose of 1.5 mg/m(2) (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m(2) q3wk and 0.58 mg/m(2) weekly, the most common adverse events were nausea, fatigue and transient neutropenia and transaminase increase.
  
  
  CONCLUSIONS
  Two different trabectedin schedules showed modest activity in metastatic CRPC. Further studies may require identification of predictive factors of response in prostate cancer.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, USA. Electronic address: dmichaelson1@partners.org.
authors.forename: M D
authors.initials: MD
authors.lastname: Michaelson
authors.affiliation: Medical Oncology Service, Hospital del Mar, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia.
authors.forename: G R
authors.initials: GR
authors.lastname: Hudes
authors.affiliation: Department of Oncology, Montefiore-Einstein Cancer Center, Bronx.
authors.forename: S
authors.initials: S
authors.lastname: Goel
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: Department of Oncology, Montefiore-Einstein Cancer Center, Bronx.
authors.forename: C A
authors.initials: CA
authors.lastname: Stein
authors.affiliation: Clinical R&D, PharmaMar, Colmenar Viejo, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Lardelli
authors.affiliation: Clinical R&D, PharmaMar, Colmenar Viejo, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Pardos
authors.affiliation: Clinical R&D, PharmaMar, Colmenar Viejo, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Kahatt
authors.affiliation: Clinical R&D, PharmaMar, Colmenar Viejo, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Nieto
authors.affiliation: Clinical R&D, PharmaMar, Colmenar Viejo, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cullell-Young
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia.
authors.forename: N L
authors.initials: NL
authors.lastname: Lewis
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D004149:Dioxoles / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000077606:Trabectedin; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin