@article{Glasspool:2014:10.1038/bjc.2014.116,
author = {Glasspool, RM and Brown, R and Gore, ME and Rustin, GJS and McNeish, IA and Wilson, RH and Pledge, S and Paul, J and Mackean, M and Hall, GD and Gabra, H and Halford, SER and Walker, J and Appleton, K and Ullah, R and Kaye, S},
doi = {10.1038/bjc.2014.116},
journal = {British Journal of Cancer},
pages = {1923--1929},
title = {A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2 '-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer},
url = {http://dx.doi.org/10.1038/bjc.2014.116},
volume = {110},
year = {2014}
}

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TY  - JOUR
AB  - Background: Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance inovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-20-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer.Methods: Patients progressing 6–12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) onday 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma.Results: After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated withthe combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin andcarboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatinhypersensitivity (47% vs 21%).Conclusions: With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partiallyplatinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents shouldbe considered in future combination studies.
AU  - Glasspool,RM
AU  - Brown,R
AU  - Gore,ME
AU  - Rustin,GJS
AU  - McNeish,IA
AU  - Wilson,RH
AU  - Pledge,S
AU  - Paul,J
AU  - Mackean,M
AU  - Hall,GD
AU  - Gabra,H
AU  - Halford,SER
AU  - Walker,J
AU  - Appleton,K
AU  - Ullah,R
AU  - Kaye,S
DO  - 10.1038/bjc.2014.116
EP  - 1929
PY  - 2014///
SN  - 1532-1827
SP  - 1923
TI  - A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2 '-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer
T2  - British Journal of Cancer
UR  - http://dx.doi.org/10.1038/bjc.2014.116
UR  - http://hdl.handle.net/10044/1/25705
VL  - 110
ER  - 

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