Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: The phase III OVATURE multicenter randomized study

C. Fotopoulou, I. Vergote, P. Mainwaring, M. Bidzinski, J. B. Vermorken, Sharad A Ghamande, P. Harnett, S. A. del Prete, J. A. Green, M. Spaczynski, S. Blagden, M. Gore, J. Ledermann, S. Kaye, H. Gabra

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95% CI = 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% CI 32.0-45.3) versus 45.7 weeks (95% CI 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.

Original languageEnglish (US)
Article numbermdt515
Pages (from-to)160-165
Number of pages6
JournalAnnals of Oncology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2014

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Carboplatin
Platinum
Ovarian Neoplasms
Multicenter Studies
Confidence Intervals
Disease-Free Survival
Survival Rate
Placebos
Cytotoxins
Immunologic Factors
Patient Selection
phenoxodiol
Quality of Life
Therapeutics
Population

Keywords

  • Carboplatin
  • Ovarian cancer relapse
  • Phenoxodiol
  • Platinum resistance
  • Reversal
  • Survival

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity : The phase III OVATURE multicenter randomized study. / Fotopoulou, C.; Vergote, I.; Mainwaring, P.; Bidzinski, M.; Vermorken, J. B.; Ghamande, Sharad A; Harnett, P.; del Prete, S. A.; Green, J. A.; Spaczynski, M.; Blagden, S.; Gore, M.; Ledermann, J.; Kaye, S.; Gabra, H.

In: Annals of Oncology, Vol. 25, No. 1, mdt515, 01.01.2014, p. 160-165.

Research output: Contribution to journalArticle

Fotopoulou, C, Vergote, I, Mainwaring, P, Bidzinski, M, Vermorken, JB, Ghamande, SA, Harnett, P, del Prete, SA, Green, JA, Spaczynski, M, Blagden, S, Gore, M, Ledermann, J, Kaye, S & Gabra, H 2014, 'Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: The phase III OVATURE multicenter randomized study', Annals of Oncology, vol. 25, no. 1, mdt515, pp. 160-165. https://doi.org/10.1093/annonc/mdt515
Fotopoulou, C. ; Vergote, I. ; Mainwaring, P. ; Bidzinski, M. ; Vermorken, J. B. ; Ghamande, Sharad A ; Harnett, P. ; del Prete, S. A. ; Green, J. A. ; Spaczynski, M. ; Blagden, S. ; Gore, M. ; Ledermann, J. ; Kaye, S. ; Gabra, H. / Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity : The phase III OVATURE multicenter randomized study. In: Annals of Oncology. 2014 ; Vol. 25, No. 1. pp. 160-165.
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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 (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95{\%} CI = 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{\%} CI 32.0-45.3) versus 45.7 weeks (95{\%} CI 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.",
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T1 - Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity

T2 - The phase III OVATURE multicenter randomized study

AU - Fotopoulou, C.

AU - Vergote, I.

AU - Mainwaring, P.

AU - Bidzinski, M.

AU - Vermorken, J. B.

AU - Ghamande, Sharad A

AU - Harnett, P.

AU - del Prete, S. A.

AU - Green, J. A.

AU - Spaczynski, M.

AU - Blagden, S.

AU - Gore, M.

AU - Ledermann, J.

AU - Kaye, S.

AU - Gabra, H.

PY - 2014/1/1

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N2 - 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 (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95% CI = 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% CI 32.0-45.3) versus 45.7 weeks (95% CI 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.

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KW - Ovarian cancer relapse

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KW - Platinum resistance

KW - Reversal

KW - Survival

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