Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial
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Published:2023-07-07
Issue:4
Volume:129
Page:706-720
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ISSN:0007-0920
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Container-title:British Journal of Cancer
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language:en
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Short-container-title:Br J Cancer
Author:
Joharatnam-Hogan Nalinie, Hatem Duaa, Cafferty Fay H., Petrucci Giovanna, Cameron David A.ORCID, Ring AlistairORCID, Kynaston Howard G., Gilbert Duncan C., Wilson Richard H.ORCID, Hubner Richard A., Swinson Daniel E. B.ORCID, Cleary SiobhanORCID, Robbins Alex, MacKenzie Mairead, Scott-Brown Martin W. G., Sothi Sharmila, Dawson Lesley K., Capaldi Lisa M., Churn Mark, Cunningham DavidORCID, Khoo Vincent, Armstrong Anne C., Ainsworth Nicola L., Horan Gail, Wheatley Duncan A., Mullen Russell, Lofts Fiona J.ORCID, Walther Axel, Herbertson Rebecca A., Eaton John D., O’Callaghan Ann, Eichholz Andrew, Kagzi Mohammed M., Patterson Daniel M., Narahari Krishna, Bradbury Jennifer, Stokes Zuzana, Rizvi Azhar J., Walker Georgina A., Kunene Victoria L., Srihari Narayanan, Gentry-Maharaj Aleksandra, Meade AngelaORCID, Patrono Carlo, Rocca Bianca, Langley Ruth E.ORCID
Abstract
Abstract
Background
Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases.
Methods
Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values.
Results
In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77–82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg.
Conclusions
Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.
Funder
Cancer Research UK DH | National Institute for Health Research RCUK | Medical Research Council
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
Reference64 articles.
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