title: Referrals to phase I clinical trials in a gynecologic oncology unit.
abstract: OBJECTIVE
  Previous reviews of phase I clinical trials report limited response rates. Development of novel biologic agents and trials designs have increased these rates. A contemporary appraisal of phase I clinical trials in gynecologic malignancies could help validate these findings.
  
  
  METHODS
  Retrospectively reviewed records for 410 patients with gynecologic malignancies treated in a phase I unit, January 1999 to October 2012. Patient characteristics and treatment outcomes were abstracted and analyzed.
  
  
  RESULTS
  Patients enrolled in 43 different phase I trials, 17 phase Ia, 17 phase Ib dose escalation and 9 dose expansion. 9 trials (21%) investigated unique cytotoxic delivery methods, 15 (35%) conventional cytotoxic plus novel agents and 19 (44%) novel agents alone. For patients treated in the first-line setting, 90 (74.4%) achieved CR, 20 (16.5%) PR, 9 (7.4%) SD and 2 (1.7%) PD, yielding an overall response rate of 90.9%. In patients treated for recurrent disease, 2 (1.6%) achieved CR, 11 (8.9%) PR, 57 (46.0%) SD and 54 (43.5%) PD, yielding a response rate of 11% and an overall clinical benefit rate of 57%. Response rate for molecular targeted therapies was 11.5% with an overall clinical benefit rate of 46.2%. Patients with prior anti-angiogenic exposure had comparable median PFS to those who had not been previously exposed (3.5 vs. 4.0 months, p = 0.29).
  
  
  CONCLUSIONS
  Results support referral of gynecologic cancer patients for phase I clinical trials. Patients with advanced, heavily pretreated disease fare at least as well as they do on phase II trials and a proportion of them can attain an objective response or stabilization of their disease.
authors.affiliation: University of Oklahoma Health Sciences Center, USA. Electronic address: Katrina-slaughter@ouhsc.edu.
authors.forename: Katrina N
authors.initials: KN
authors.lastname: Slaughter
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Nugent
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Erin A
authors.initials: EA
authors.lastname: Bishop
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Latoya J
authors.initials: LJ
authors.lastname: Perry
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: D Scott
authors.initials: DS
authors.lastname: McMeekin
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D005833:Genital Neoplasms, Female / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008875:Middle Aged; D012017:Referral and Consultation; D012189:Retrospective Studies
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Phase I; Platinum resistant; Targeted therapy