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.
Author(s): Baumann KH, du Bois A, Meier W, Rau J, Wimberger P, Sehouli J, Kurzeder C,
Hilpert F, Hasenburg A, Canzler U, Hanker LC, Hillemanns P, Richter B,
Wollschlaeger K, Dewitz T, Bauerschlag D, Wagner U.
Affiliation(s): Department of Gynaecology, University of Marburg, Marburg, Germany.
baumannk@med.uni-marburg.de
Publication date & source: 2012, Ann Oncol. , 23(9):2265-71
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.
MATERIAL AND 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.
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