eprintid: 10092744
rev_number: 15
eprint_status: archive
userid: 608
dir: disk0/10/09/27/44
datestamp: 2020-03-10 14:45:50
lastmod: 2021-09-25 23:31:38
status_changed: 2020-03-10 14:45:50
type: article
metadata_visibility: show
creators_name: Oza, AM
creators_name: Matulonis, UA
creators_name: Alvarez Secord, A
creators_name: Nemunaitis, J
creators_name: Roman, LD
creators_name: Blagden, SP
creators_name: Banerjee, S
creators_name: McGuire, WP
creators_name: Ghamande, S
creators_name: Birrer, MJ
creators_name: Fleming, GF
creators_name: Markham, MJ
creators_name: Hirte, HW
creators_name: Provencher, DM
creators_name: Basu, B
creators_name: Kristeleit, R
creators_name: Armstrong, DK
creators_name: Schwartz, B
creators_name: Braly, P
creators_name: Hall, GD
creators_name: Nephew, KP
creators_name: Jueliger, S
creators_name: Oganesian, A
creators_name: Naim, S
creators_name: Hao, Y
creators_name: Keer, H
creators_name: Azab, M
creators_name: Matei, D
title: A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D19
divisions: G99
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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/m^{2} 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.
date: 2020-03
date_type: published
official_url: https://doi.org/10.1158/1078-0432.CCR-19-1638
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1731661
doi: 10.1158/1078-0432.CCR-19-1638
pii: 1078-0432.CCR-19-1638
lyricists_name: Kristeleit, Rebecca
lyricists_id: RSKRI39
actors_name: Kristeleit, Rebecca
actors_id: RSKRI39
actors_role: owner
full_text_status: public
publication: Clinical Cancer Research
volume: 26
number: 5
pagerange: 1009-1016
event_location: United States
issn: 1078-0432
citation:        Oza, AM;    Matulonis, UA;    Alvarez Secord, A;    Nemunaitis, J;    Roman, LD;    Blagden, SP;    Banerjee, S;                                                                                     ... Matei, D; + view all <#>        Oza, AM;  Matulonis, UA;  Alvarez Secord, A;  Nemunaitis, J;  Roman, LD;  Blagden, SP;  Banerjee, S;  McGuire, WP;  Ghamande, S;  Birrer, MJ;  Fleming, GF;  Markham, MJ;  Hirte, HW;  Provencher, DM;  Basu, B;  Kristeleit, R;  Armstrong, DK;  Schwartz, B;  Braly, P;  Hall, GD;  Nephew, KP;  Jueliger, S;  Oganesian, A;  Naim, S;  Hao, Y;  Keer, H;  Azab, M;  Matei, D;   - view fewer <#>    (2020)    A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.                   Clinical Cancer Research , 26  (5)   pp. 1009-1016.    10.1158/1078-0432.CCR-19-1638 <https://doi.org/10.1158/1078-0432.CCR-19-1638>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10092744/1/Guadecitabine%20and%20carboplatin%20in%20ovarian%20cancer.pdf