Imperial College London
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Professor Mona El-Bahrawy

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Practice (Histopathology)
 
 
 
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Contact

 

m.elbahrawy

 
 
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Location

 

Department of HistopathologyHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Blagden:2018:10.1038/s41416-018-0244-1,
author = {Blagden, SP and Rizzuto, I and Suppiah, P and O'Shea, D and Patel, M and Spiers, L and Sukumaran, A and Bharwani, N and Rockall, A and Gabra, H and El-Bahrawy, M and Wasan, H and Leonard, R and Habib, N and Ghazaly, E},
doi = {10.1038/s41416-018-0244-1},
journal = {British Journal of Cancer},
pages = {815--822},
title = {Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study},
url = {http://dx.doi.org/10.1038/s41416-018-0244-1},
volume = {119},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundGemcitabine is used to treat a wide range of tumours, but its efficacy is limited by cancer cell resistance mechanisms. NUC-1031, a phosphoramidate modification of gemcitabine, is the first anti-cancer ProTide to enter the clinic and is designed to overcome these key resistance mechanisms.MethodsSixty-eight patients with advanced solid tumours who had relapsed after treatment with standard therapy were recruited to a dose escalation study to determine the recommended Phase II dose (RP2D) and assess the safety of NUC-1031. Pharmacokinetics and anti-tumour activity was also assessed.ResultsSixty-eight patients received treatment, 50% of whom had prior exposure to gemcitabine. NUC-1031 was well tolerated with the most common Grade 3/4 adverse events of neutropaenia, lymphopaenia and fatigue occurring in 13 patients each (19%). In 49 response-evaluable patients, 5 (10%) achieved a partial response and 33 (67%) had stable disease, resulting in a 78% disease control rate. Cmax levels of the active intracellular metabolite, dFdCTP, were 217-times greater than those reported for equimolar doses of gemcitabine, with minimal toxic metabolite accumulation. The RP2D was determined as 825 mg/m2 on days 1, 8 and 15 of a 28-day cycle.ConclusionsNUC-1031 was well tolerated and demonstrated clinically significant anti-tumour activity, even in patients with prior gemcitabine exposure and in cancers not traditionally perceived as gemcitabine-responsive.
AU  - Blagden,SP
AU  - Rizzuto,I
AU  - Suppiah,P
AU  - O'Shea,D
AU  - Patel,M
AU  - Spiers,L
AU  - Sukumaran,A
AU  - Bharwani,N
AU  - Rockall,A
AU  - Gabra,H
AU  - El-Bahrawy,M
AU  - Wasan,H
AU  - Leonard,R
AU  - Habib,N
AU  - Ghazaly,E
DO  - 10.1038/s41416-018-0244-1
EP  - 822
PY  - 2018///
SN  - 0007-0920
SP  - 815
TI  - Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study
T2  - British Journal of Cancer
UR  - http://dx.doi.org/10.1038/s41416-018-0244-1
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000447291900006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/63925
VL  - 119
ER  -
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