title: Sorafenib in combination with carboplatin and paclitaxel as neoadjuvant chemotherapy in patients with advanced ovarian cancer.
abstract: OBJECTIVE
  Sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways through inhibitory effects against MAP kinases and vascular endothelial growth factor receptor-2. The objectives of this neoadjuvant phase II-trial in patients with advanced epithelial ovarian cancer were to assess the activity and tolerability of the combination therapy of carboplatin/paclitaxel with multi-target tyrosine kinase inhibitor sorafenib.
  
  
  METHODS
  Patients with histologically proven stage IIIC or IV disease and large volume ascites were eligible. Enrolled patients received 2 of 6 cycles carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2)) preoperatively and concomitant sorafenib 400 mg twice daily. After four cycles of postoperative chemotherapy, a maintenance phase of single agent oral sorafenib through 1 year was planned. This phase II-study was planned with a sample size of 102 patients and progression-free survival as primary study endpoint.
  
  
  RESULTS
  Four patients were enrolled. After preoperative treatment and cytoreductive surgery, all patients were excluded from protocol due to severe toxicities. Three patients had life threatening events (cardiac output failure, myocardial infarction, anastomotic leak); two patients had primary progressive disease. The study was terminated on the basis of the recommendation of an independent data safety monitoring board.
  
  
  CONCLUSIONS
  The addition of sorafenib to carboplatin/paclitaxel chemotherapy was not feasible within this neoadjuvant regimen in primary advanced ovarian cancer. Although the occurrence of serious adverse events might have emerged at random, a detrimental effect of preoperative study medication could not be denied. Further evaluations of sorafenib in ovarian cancer are warranted.
authors.affiliation: Department of Gynecology and Obstetrics, Center for Integrated Oncology, Bonn University Medical Center, University Hospital of Bonn, Sigmund-Freud-Str 25, 53105 Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Pölcher
authors.forename: Meike
authors.initials: M
authors.lastname: Eckhardt
authors.forename: Christoph
authors.initials: C
authors.lastname: Coch
authors.forename: Matthias
authors.initials: M
authors.lastname: Wolfgarten
authors.forename: Kirsten
authors.initials: K
authors.lastname: Kübler
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.forename: Christian
authors.initials: C
authors.lastname: Rudlowski
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage*; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality; D009536:Niacinamide / Q000031:analogs & derivatives; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage*; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D000077157:Sorafenib
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D016190:Carboplatin; D017239:Paclitaxel