title: A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy.
abstract: BACKGROUND
  Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted. This phase II study was conducted to evaluate sunitinib, an oral antiangiogenic multitargeted tyrosin kinase inhibitor, in this setting.
  
  
  METHODS
  The primary end point of this randomized phase II trial was the objective response rate according to RECIST criteria and/or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies. A selection design was employed to compare two schedules of sunitinib (arm 1: 50 mg sunitinib daily orally for 28 days followed by 14 days off drug; and arm 2: 37.5 mg sunitinib administered daily continuously).
  
  
  RESULTS
  Of 73 patients enrolled, 36 patients were randomly allocated to the noncontinuous treatment arm (arm 1) and 37 patients were randomly allocated to the continuous treatment arm (arm 2). The mean age was 58.8 and 58.5 years, respectively. We observed six responders (complete response + partial response) in arm 1 (16.7%) and 2 responders in arm 2 (5.4%). The median progression-free survival (arm 1: 4.8 [2.9-8.1] months; arm 2: 2.9 [2.9-5.1] months) and the median overall survival (arm 1: 13.6 [7.0-23.2] months; arm 2: 13.7 [8.4-25.6] months) revealed no significant difference. Adverse events included fatigue as well as cardiovascular, gastrointestinal and abdominal symptoms, hematologic and hepatic laboratory abnormalities. Pattern and frequency of adverse events revealed no substantial differences between both treatment groups.
  
  
  CONCLUSIONS
  Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer. The noncontinuous treatment schedule should be chosen for further studies in ovarian cancer.
authors.affiliation: Department of Gynaecology, University of Marburg, Marburg. Electronic address: baumannk@med.uni-marburg.de.
authors.forename: K H
authors.initials: KH
authors.lastname: Baumann
authors.affiliation: Department of Gynaecology and Gynaecological Oncology, HSK Wiesbaden and Kliniken Essen Mitte, Essen.
authors.forename: A
authors.initials: A
authors.lastname: du Bois
authors.affiliation: Department of Gynaecology and Obstetrics, Evangelic Hospital, Duesseldorf.
authors.forename: W
authors.initials: W
authors.lastname: Meier
authors.affiliation: Coordinating Centre for Clinical Trials, University of Marburg, Marburg.
authors.forename: J
authors.initials: J
authors.lastname: Rau
authors.affiliation: Department of Gynaecology and Obstetrics, University of Duisburg-Essen, Essen.
authors.forename: P
authors.initials: P
authors.lastname: Wimberger
authors.affiliation: Department of Gynaecology, Charité, Berlin.
authors.forename: J
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Department of Gynaecology and Obstetrics, University of Ulm, Ulm.
authors.forename: C
authors.initials: C
authors.lastname: Kurzeder
authors.affiliation: Department of Gynaecology and Obstetrics, University of Kiel, Kiel.
authors.forename: F
authors.initials: F
authors.lastname: Hilpert
authors.affiliation: Department of Gynaecology and Obstetrics, University of Freiburg, Freiburg.
authors.forename: A
authors.initials: A
authors.lastname: Hasenburg
authors.affiliation: Department of Gynaecology and Obstetrics, University of Dresden, Dresden.
authors.forename: U
authors.initials: U
authors.lastname: Canzler
authors.affiliation: Department of Gynaecology and Obstetrics, University of Frankfurt am Main, Frankfurt am Main.
authors.forename: L C
authors.initials: LC
authors.lastname: Hanker
authors.affiliation: Department of Gynaecology and Obstetrics, Medical School Hannover, Hannover.
authors.forename: P
authors.initials: P
authors.lastname: Hillemanns
authors.affiliation: Department of Gynaecology and Obstetrics, Elbland Hospital, Radebeul.
authors.forename: B
authors.initials: B
authors.lastname: Richter
authors.affiliation: Department of Gynaecology and Obstetrics, University of Magdeburg, Magdeburg.
authors.forename: K
authors.initials: K
authors.lastname: Wollschlaeger
authors.affiliation: Department of Gynaecology and Obstetrics, Hospital of Gifhorn, Gifhorn.
authors.forename: T
authors.initials: T
authors.lastname: Dewitz
authors.affiliation: Department of Gynaecology and Obstetrics, University Medical Center Aachen RWTH, Aachen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Bauerschlag
authors.affiliation: Department of Gynaecology, University of Marburg, Marburg.
authors.forename: U
authors.initials: U
authors.lastname: Wagner
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017671:Platinum Compounds / Q000494:pharmacology; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D017671:Platinum Compounds; D011758:Pyrroles; D020794:Receptor Protein-Tyrosine Kinases; D000077210:Sunitinib