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Gemcitabine and Platinum-Based Agents for the Prediction of Cancer-Associated Venous Thromboembolism: Results from the Vienna Cancer and Thrombosis Study

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Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria
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Department of Vascular Medicine, Amsterdam Academic Medical Center, 1105 Amsterdam, The Netherlands
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Division of Oncology, Department of Internal Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria
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Department of Medicine and Ageing Sciences, University G. D’Annunzio, 66100 Chieti, Italy
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Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria
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I. M. Sechenov First Moscow State Medical University, 119146 Moscow, Russia
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Author to whom correspondence should be addressed.
Cancers 2020, 12(9), 2493; https://doi.org/10.3390/cancers12092493
Received: 15 July 2020 / Revised: 28 August 2020 / Accepted: 1 September 2020 / Published: 3 September 2020
(This article belongs to the Section Cancer Therapy)
Certain chemotherapy agents (gemcitabine, platinum-based agents) have been suggested to increase the risk of venous thromboembolism in cancer patients. Our aim was to evaluate, whether treatment with these agents can be used to better predict the risk of cancer-associated venous thromboembolism. Within a prospective observational cohort study, including 1409 patients, we found that treatment with gemcitabine and/or platinum-based agents is only of limited value in predicting the risk of venous thromboembolism beyond known risk factors included in an established risk prediction model (tumor type, blood levels of D-dimer). These findings suggest that a large part of the observed rate of venous thromboembolism in patients treated with these agents might be related to the underlying thrombotic risk rather than the agent itself.
Gemcitabine and platinum-based agents could increase the risk of venous thromboembolism (VTE) in patients with cancer. We evaluated the additive predictive utility of these agents towards cancer-associated VTE beyond a recently developed and externally validated clinical prediction model, which was based on tumor entity and continuous D-dimer levels. Analysis was performed in the derivation cohort of this model, obtained from the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study (n = 1409). Patients were followed for the occurrence of VTE for a maximum of two years. Competing-risk analysis was performed to obtain cumulative incidences and to conduct between-group comparisons of VTE risk. Cumulative two-year incidences of VTE were not elevated with gemcitabine treatment (10.2% vs. 7.5%, p = 0.148), whereas they were higher for platinum-based therapy (11.6% vs. 5.9%, p < 0.001). In a multivariable analysis, adjusting for tumor site category and D-dimer, gemcitabine was not associated with increased risk of VTE (subdistribution hazard ratio (SHR) 0.82, 95% confidence interval (CI) 0.53–1.28, p = 0.390), whereas platinum-based therapy predicted for a numerically increased VTE risk (SHR 1.44, 95% CI 0.96–2.17, p = 0.080). Similar results were obtained in a sensitivity analysis (updated cohort, n = 1870). Our findings suggest limited additional value of chemotherapy for the prediction of cancer-associated VTE, beyond a validated clinical prediction model. View Full-Text
Keywords: cancer; venous thromboembolism; chemotherapy; gemcitabine; platinum compounds cancer; venous thromboembolism; chemotherapy; gemcitabine; platinum compounds
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MDPI and ACS Style

Moik, F.; van Es, N.; Posch, F.; Di Nisio, M.; Fuereder, T.; Preusser, M.; Pabinger, I.; Ay, C. Gemcitabine and Platinum-Based Agents for the Prediction of Cancer-Associated Venous Thromboembolism: Results from the Vienna Cancer and Thrombosis Study. Cancers 2020, 12, 2493. https://doi.org/10.3390/cancers12092493

AMA Style

Moik F, van Es N, Posch F, Di Nisio M, Fuereder T, Preusser M, Pabinger I, Ay C. Gemcitabine and Platinum-Based Agents for the Prediction of Cancer-Associated Venous Thromboembolism: Results from the Vienna Cancer and Thrombosis Study. Cancers. 2020; 12(9):2493. https://doi.org/10.3390/cancers12092493

Chicago/Turabian Style

Moik, Florian, Nick van Es, Florian Posch, Marcello Di Nisio, Thorsten Fuereder, Matthias Preusser, Ingrid Pabinger, and Cihan Ay. 2020. "Gemcitabine and Platinum-Based Agents for the Prediction of Cancer-Associated Venous Thromboembolism: Results from the Vienna Cancer and Thrombosis Study" Cancers 12, no. 9: 2493. https://doi.org/10.3390/cancers12092493

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