Title
Weekly AUC2 carboplatin in acquired platinum resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity : the phase Ill OVATURE multicenter randomized studyWeekly AUC2 carboplatin in acquired platinum resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity : the phase Ill OVATURE multicenter randomized study
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO)
Publication type
article
Publication
Amsterdam,
Subject
Human medicine
Source (journal)
Annals of oncology / European Society for Medical Oncology. - Amsterdam
Volume/pages
25(2014):1, p. 160-165
ISSN
0923-7534
ISI
000331268800025
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background: Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients. Patients and methods: A multicenter randomized double-blind placebo controlled phase-III-study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end point was progression-free-survival (PFS). Secondary objectives included overall survival (OS), response rates, duration of response and quality of life. Results: The study was terminated early 14 April 2009, after recruitment of 142 patients due to feasibility and recruitment challenges. A total of 142 patients were randomized. The groups were well balanced in terms of important baseline characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence interval (Cl) 11.1-21.0] versus 20.1 weeks for group 2 (95% Cl 13.1-33.4); P 0.3. The objective response rate and median survival in group 1 versus group 2 was 0% versus 1% and 38.3 weeks (95% Cl 32.0-45.3) versus 45.7 weeks (95% Cl 35.6-58.0), respectively. PXD appeared to be well tolerated. The main reason for dose modification in both groups was hematologic toxicity. Conclusions: Orally delivered PXD showed no evidence of clinical activity, when combined with weekly AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin appeared to be inactive by response criteria in a homogenously defined population of PROC. This has implications for the design of future studies. Clinicaltrials.gov identifier: NCT00382811.
E-info
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000331268800025&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000331268800025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000331268800025&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle