title: Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer.
abstract: OBJECTIVE
  This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinum-sensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC).
  
  
  METHODS
  Patients with recurrent platinum-sensitive EOC with no more than 2 prior courses of chemotherapy were randomized to single-agent sorafenib 400 mg twice daily or combination sorafenib 400 mg bid (days 2-19) with IV carboplatin (AUC 6) and IV paclitaxel 175 mg/m(2) (S+C/T) every 3 weeks. Single agent sorafenib could cross over to combination upon progression.
  
  
  RESULTS
  Patients were initially randomized to either arm, however, due to poor accrual, sorafenib arm was prematurely closed. A total of 13 patients were evaluable for response to sorafenib and 23 patients were evaluable for response to S+C/T. Objective response rate (RR) was 15 % for patients on sorafenib vs. 61 % for patients on S+C/T (p = 0.014); stable disease was seen in 62 % and 35 %, respectively. Clinical benefit rate (CBR) at 4 months (mos.) was 69 % for S and 65 % for S+C/T. The median progression free survival was 5.6 months on sorafenib vs. 16.8 months on S+C/T (p = 0.012) and there was no significant difference of overall survival between two arms (p = 0.974) with median overall survival 25.6 months under sorafenib vs. 25.9 months on S+C/T. Patients remained on trial for a median of 7.8 cycles on sorafenib and 5.4 cycles on S+C/T.
  
  
  CONCLUSIONS
  Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinum-sensitive EOC. Sorafenib in combination with carboplatin and paclitaxel improved RR and PFS; however, there were increased grade and frequencies of toxicities.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Schwandt
authors.forename: Vivian E
authors.initials: VE
authors.lastname: von Gruenigen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Wenham
authors.forename: Heidi
authors.initials: H
authors.lastname: Frasure
authors.forename: Susan
authors.initials: S
authors.lastname: Eaton
authors.forename: Nancy
authors.initials: N
authors.lastname: Fusco
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Steven
authors.initials: S
authors.lastname: Waggoner
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D016190:Carboplatin; D017239:Paclitaxel