Danson, S. orcid.org/0000-0002-3593-2890, Mulvey, M.R., Turner, L. et al. (6 more authors) (2019) An exploratory randomized-controlled trial of the efficacy of the Src-kinase inhibitor saracatinib as a novel analgesic for cancer-induced bone pain. Journal of Bone Oncology, 19. 100261. ISSN 2212-1374
Abstract
Pain is a major symptom of bone metastases from advanced cancer and represents a clinical challenge to treat effectively. Basic neurobiology in preclinical animal models implicates enhanced sensory processing in the central nervous system, acting through N-methyl-D-aspartate (NMDA) glutamate receptors, as an important mechanism underpinning persistent pain. The non-receptor tyrosine kinase Src is thought to act as a hub for regulating NMDA receptor activity and the orally available Src inhibitor saracatinib has shown promise as a potential analgesic in recent animal studies. Here we tested the efficacy of saracatinib as a novel analgesic in an exploratory phase II randomized controlled trial on cancer patients with painful bone metastases. Twelve patients completed the study, with 6 receiving saracatinib 125mg/day for 28 days and 6 receiving placebo. Pharmacokinetic measurements confirmed appropriate plasma levels of drug in the saracatinib-treated group and Src inhibition was achieved clinically by a significant reduction in the bone resorption biomarker serum cross-linked C-terminal telopeptide of type I collagen. Differences between the saracatinib and placebo groups self-reported pain scores, measured using the short form of the Brief Pain Inventory, were not clinically significant after 4 weeks of treatment. There was also no change in consumption of maintenance analgesia in the saracatinib-treated group and no improvement in Quality – of - Life scores. The data were insufficient to demonstrate saracatinib has efficacy as analgesic, although it may have a role as an anti-bone resorptive agent.
Metadata
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Copyright, Publisher and Additional Information: | © 2019 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/). | ||||
Keywords: | Cancer pain; Src inhibitor; Metastasis; Clinical trial; Saracatinib | ||||
Dates: |
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Institution: | The University of Sheffield | ||||
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
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Funding Information: |
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Depositing User: | Symplectic Sheffield | ||||
Date Deposited: | 24 Sep 2019 11:03 | ||||
Last Modified: | 16 Dec 2021 10:01 | ||||
Status: | Published | ||||
Publisher: | Elsevier | ||||
Refereed: | Yes | ||||
Identification Number: | https://doi.org/10.1016/j.jbo.2019.100261 |