dc.contributor.author |
Spiegelberg, L |
en |
dc.contributor.author |
Houben, R |
en |
dc.contributor.author |
Niemans, R |
en |
dc.contributor.author |
de Ruysscher, D |
en |
dc.contributor.author |
Yaromina, A |
en |
dc.contributor.author |
Theys, J |
en |
dc.contributor.author |
Guise, CP |
en |
dc.contributor.author |
Smaill, Jeffrey |
en |
dc.contributor.author |
Patterson, Adam |
en |
dc.contributor.author |
Lambin, P |
en |
dc.contributor.author |
Dubois, L |
en |
dc.date.accessioned |
2019-06-13T03:20:34Z |
en |
dc.date.issued |
2019-02 |
en |
dc.identifier.citation |
Clinical and Translational Radiation Oncology 15:62-69 Feb 2019 |
en |
dc.identifier.issn |
2405-6308 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/47023 |
en |
dc.description.abstract |
Hypoxia-activated prodrugs (HAPs) are designed to specifically target the hypoxic cells of tumors, which are an important cause of treatment resistance to conventional therapies. Despite promising preclinical and clinical phase I and II results, the most important of which are described in this review, the implementation of hypoxia-activated prodrugs in the clinic has, so far, not been successful. The lack of stratification of patients based on tumor hypoxia status, which can vary widely, is sufficient to account for the failure of phase III trials. To fully exploit the potential of hypoxia-activated prodrugs, hypoxia stratification of patients is needed. Here, we propose a biomarker-stratified enriched Phase III study design in which only biomarker-positive (i.e. hypoxia-positive) patients are randomized between standard treatment and the combination of standard treatment with a hypoxia-activated prodrug. This implies the necessity of a Phase II study in which the biomarker or a combination of biomarkers will be evaluated. The total number of patients needed for both clinical studies will be far lower than in currently used randomize-all designs. In addition, we elaborate on the improvements in HAP design that are feasible to increase the treatment success rates. |
en |
dc.publisher |
Elsevier |
en |
dc.relation.ispartofseries |
Clinical and Translational Radiation Oncology |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
en |
dc.title |
Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.ctro.2019.01.005 |
en |
pubs.begin-page |
62 |
en |
pubs.volume |
15 |
en |
dc.rights.holder |
Copyright: the authors |
en |
pubs.end-page |
69 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Review |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
761532 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2019-02-14 |
en |
pubs.online-publication-date |
2019-01-18 |
en |