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A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.


ABSTRACT:

Purpose

Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer.

Patients and methods

Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS).

Results

Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group.

Conclusions

Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.

SUBMITTER: Oza AM 

PROVIDER: S-EPMC7056559 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

Oza Amit M AM   Matulonis Ursula A UA   Alvarez Secord Angeles A   Nemunaitis John J   Roman Lynda D LD   Blagden Sarah P SP   Banerjee Susana S   McGuire William P WP   Ghamande Sharad S   Birrer Michael J MJ   Fleming Gini F GF   Markham Merry Jennifer MJ   Hirte Hal W HW   Provencher Diane M DM   Basu Bristi B   Kristeleit Rebecca R   Armstrong Deborah K DK   Schwartz Benjamin B   Braly Patricia P   Hall Geoff D GD   Nephew Kenneth P KP   Jueliger Simone S   Oganesian Aram A   Naim Sue S   Hao Yong Y   Keer Harold H   Azab Mohammad M   Matei Daniela D  

Clinical cancer research : an official journal of the American Association for Cancer Research 20191212 5


<h4>Purpose</h4>Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer.<h4>Patients and methods</h4>Patients received either G+C (guadecitabine 30 mg/m<sup>2</sup  ...[more]

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