A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Azacitidine
/ administration & dosage
Carboplatin
/ administration & dosage
Deoxycytidine
/ administration & dosage
Doxorubicin
/ administration & dosage
Drug Resistance, Neoplasm
/ drug effects
Epigenesis, Genetic
/ drug effects
Female
Humans
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Ovarian Neoplasms
/ drug therapy
Paclitaxel
/ administration & dosage
Patient Safety
Polyethylene Glycols
/ administration & dosage
Survival Rate
Topotecan
/ administration & dosage
Treatment Outcome
Gemcitabine
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
received:
30
05
2019
revised:
16
09
2019
accepted:
05
12
2019
pubmed:
14
12
2019
medline:
5
1
2021
entrez:
14
12
2019
Statut:
ppublish
Résumé
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 received either G+C (guadecitabine 30 mg/m 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; 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.
Identifiants
pubmed: 31831561
pii: 1078-0432.CCR-19-1638
doi: 10.1158/1078-0432.CCR-19-1638
pmc: PMC7056559
mid: NIHMS1546537
doi:
Substances chimiques
liposomal doxorubicin
0
Deoxycytidine
0W860991D6
guadecitabine
2KT4YN1DP7
Polyethylene Glycols
3WJQ0SDW1A
Topotecan
7M7YKX2N15
Doxorubicin
80168379AG
Carboplatin
BG3F62OND5
Azacitidine
M801H13NRU
Paclitaxel
P88XT4IS4D
Gemcitabine
0
Banques de données
ClinicalTrials.gov
['NCT01696032']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1009-1016Subventions
Organisme : NCI NIH HHS
ID : R01 CA182832
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
Références
Cancer Lett. 2006 Sep 28;241(2):213-20
pubmed: 16303245
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
J Clin Oncol. 2014 May 1;32(13):1302-8
pubmed: 24637997
J Clin Oncol. 2005 Jun 10;23(17):3948-56
pubmed: 15883410
BMC Med Genomics. 2008 Sep 30;1:47
pubmed: 18826610
Adv Exp Med Biol. 2008;622:35-51
pubmed: 18546617
N Engl J Med. 2005 Mar 24;352(12):1268-9; author reply 1268-9
pubmed: 15791705
Epigenetics. 2015;10(8):736-48
pubmed: 26098711
J Clin Oncol. 2007 Oct 10;25(29):4603-9
pubmed: 17925555
Gynecol Oncol. 2004 Dec;95(3):686-90
pubmed: 15581982
Cancer Immunol Res. 2014 Jan;2(1):37-49
pubmed: 24535937
Lancet Oncol. 2015 Sep;16(9):1099-1110
pubmed: 26296954
Oncotarget. 2017 Jan 10;8(2):2949-2959
pubmed: 27936464
Cancer. 2010 Sep 1;116(17):4043-53
pubmed: 20564122
Clin Cancer Res. 2018 Dec 15;24(24):6160-6167
pubmed: 30097434
Clin Cancer Res. 2014 Dec 15;20(24):6504-16
pubmed: 25316809
Cancer. 2011 Apr 15;117(8):1661-9
pubmed: 21472713
Gynecol Oncol. 2008 Apr;109(1):129-39
pubmed: 18234305
Cancer Res. 2000 Nov 1;60(21):6039-44
pubmed: 11085525
Cancer Res. 2004 Sep 15;64(18):6476-81
pubmed: 15374957
Clin Cancer Res. 2018 May 15;24(10):2285-2293
pubmed: 29500276
J Clin Oncol. 2011 Jan 10;29(2):242-8
pubmed: 21115872
Endocrinology. 2009 Sep;150(9):4003-11
pubmed: 19574400
Clin Cancer Res. 2004 Jun 1;10(11):3919-26
pubmed: 15173101
JCI Insight. 2018 Dec 6;3(23):
pubmed: 30518684
Br J Cancer. 2014 Apr 15;110(8):1923-9
pubmed: 24642620
Mol Cancer Ther. 2003 Aug;2(8):721-8
pubmed: 12939461
Cancer Res. 2018 Feb 1;78(3):631-644
pubmed: 29229600
Cancer Res. 2014 Sep 1;74(17):4922-36
pubmed: 25035395
J Clin Oncol. 2003 May 15;21(10 Suppl):187s-193s
pubmed: 12743133
Oncotarget. 2014 Jun 15;5(11):3579-89
pubmed: 25003579
Cell Cycle. 2009 Jan 1;8(1):158-66
pubmed: 19158483
Cancer Res. 2012 May 1;72(9):2197-205
pubmed: 22549947
Br J Cancer. 2002 Oct 7;87(8):815-24
pubmed: 12373593