title: Docetaxel plus trabectedin appears active in recurrent or persistent ovarian and primary peritoneal cancer after up to three prior regimens: a phase II study of the Gynecologic Oncology Group.
abstract: OBJECTIVE
  This study aims to estimate the activity of docetaxel 60mg/m(2) IV over 1h followed by trabectedin 1.1mg/m(2) over 3h with filgrastim, pegfilgrastim, or sargramostim every 3weeks (one cycle).
  
  
  METHODS
  Patients with recurrent and measurable disease, acceptable organ function, PS≤2, and ≤3 prior regimens were eligible. A two-stage design was utilized with a target sample size of 35 subjects per stage. Another Gynecologic Oncology Group study within the same protocol queue involving a single agent taxane showed a response rate (RR) of (16%) (90% CI 8.6-28.5%) and served as a historical control for direct comparison. The present study was designed to determine if the current regimen had an RR of ≥36% with 90% power.
  
  
  RESULTS
  Seventy-one patients were eligible and evaluable (prior regimens: 1=28%, 2=52%, 3=20%). The median number of cycles was 6 (438 total cycles, range 1-22). The number of patients responding was 21 (30%; 90% CI 21-40%). The odds ratio for responding was 2.2 (90% 1-sided CI 1.07-Infinity). The median progression-free survival and overall survival were 4.5months and 16.9months, respectively. The median response duration was 6.2months. Numbers of subjects with grade 3/4 toxicity included neutropenia 7/14; constitutional 8/0; GI (excluding nausea/vomiting) 11/0; metabolic 9/1; pain 6/0. There were no treatment-related deaths nor cases of liver failure.
  
  
  CONCLUSIONS
  This combination was well tolerated and appears more active than the historical control of single agent taxane therapy in those with recurrent ovarian and peritoneal cancer after failing multiple lines of chemotherapy. Further study is warranted.
authors.affiliation: Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, a Member of Catholic Healthcare West, 500 W. Thomas Road, Suite 800, Phoenix, AZ 85013, USA. Bradley.monk@chw.edu
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.forename: Parviz
authors.initials: P
authors.lastname: Hanjani
authors.forename: Robert
authors.initials: R
authors.lastname: Edwards
authors.forename: Jacob
authors.initials: J
authors.lastname: Rotmensch
authors.forename: Koen
authors.initials: K
authors.lastname: De Geest
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Bonebrake
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004149:Dioxoles / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage; D000077606:Trabectedin
chemical_list: D004149:Dioxoles; D043823:Taxoids; D044005:Tetrahydroisoquinolines; D000077143:Docetaxel; D000077606:Trabectedin