Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies
Abstract
:1. Introduction
2. Chemoprotective Effect of Aspirin
2.1. Chemoprotective Effect of Aspirin on Colorectal Cancer
2.1.1. General Population
Evidence from Epidemiological Studies
Evidence from Post-Hoc Analyses of Randomized Controlled Trials Assessing the Efficacy and Safety of Aspirin in the Prevention of Cardiovascular Disease
2.1.2. Patients at High-Risk of CRC
2.2. Chemoprotective Effect of Aspirin on Other Cancers
2.2.1. Overall Cancer Incidence
2.2.2. Overall Cancer-Related Mortality
2.3. Benefit of Aspirin as Adjuvant Treatment in Patients with Cancer
2.4. Potential Mechanisms of Action by Which Aspirin Exerts Its Anticancer Effects
3. The Chemoprotective Effect of Other Antiplatelet Agents
3.1. The Chemoprotective Effect of Other Antiplatelet Agents on the Risk of Incident Cancer
3.1.1. P2Y12 Antagonists
Evidence from Epidemiological Studies
Evidence from Secondary Analyses of Randomized Controlled Trials of Dual Antiplatelet Therapy in the Secondary Prevention of Acute Coronary Syndrome
3.1.2. Thrombin Receptor Antagonists
3.2. The Chemoprotective Effect of Other Antiplatelet Agents on the Risk of Cancer Progression
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Trial (Reference) | Study Population | Number of Subjects Randomly Assigned | Treatment Groups | Median Treatment Duration (Years) | Primary End Point | RR (95% CI) | |
---|---|---|---|---|---|---|---|
CRC Incidence | CRC-Related Mortality | ||||||
PHS [19] | Male physicians (age 40–84 years) without history of MI, stroke, cancer, liver or renal disease, gout, peptic ulcer or contraindications to aspirin | 22,071 | Placebo versus 325 mg aspirin alternate day | 5.0 | CVD and cancer | 1.03 (0.83–1.28) | Not reported |
WHS [21] | Women (age ≥ 45 years) without history of cancer (except non-melanoma skin cancer), CVD or other major chronic illness | 39,876 | Placebo versus 100 mg aspirin alternate day | 10.1 | CVD and cancer | 0.80 (0.67–0.97) | 0.80 (0.67–0.97) |
BDA [22] | Male physicians without peptic ulcer, stroke or definite MI | 5139 | Placebo versus 500 mg aspirin per day | 6.0 | CVD | 0.70 (0.51–0.97) | 0.73 (0.49–1.10) |
UK-TIA Aspirin Trial [23] | Patients with prior TIA or stroke | 2449 | Placebo versus 300 or 1200 mg aspirin per day | 4.4 | CVD | 0.75 (0.56–0.97), [25] pooled with TPT and SALT | 0.61 (0.43–0.87), [25] pooled with TPT and SALT |
TPT [41] | High risk for IHD | 5085 | Placebo versus 75 mg aspirin per day (alone or with warfarin) | 6.9 | CVD | 0.75 (0.56–0.97), [25] pooled with UK-TIA and SALT | 0.61 (0.43–0.87), [25] pooled with UK-TIA and SALT |
SALT [42] | Prior TIA or stroke or retinal occlusion | 1363 | Placebo versus 75 mg aspirin per day | 2.7 | CVD | 0.75 (0.56–0.97), [25] pooled with TPT and UK-TIA | 0.61 (0.43–0.87), [25] pooled with TPT and UK-TIA |
Trial (Reference) | Study Population | Number of Subjects Randomly Assigned | Treatment Groups | Median Follow-Up Duration (Years) | Primary End Point | RR (95% CI) | |
---|---|---|---|---|---|---|---|
Any Adenoma | Advanced ADENOMA | ||||||
AFPPS [33] | Recent history of resected sporadic colorectal adenoma | 1121 | Placebo versus 81 mg aspirin per day versus 325 mg aspirin per day, with or without folic acid | 3.0 | Recurrent adenoma | 0.88 (0.77–1.02) | 0.74 (0.52–1.06) |
CALGB [34] | Previous resection of Dukes’ stage A or B1 CRC or B2 CRC and 5-year disease-free survival | 635 | Placebo versus 325 mg aspirin per day | 1.1 | Adenoma | 0.61 (0.44–0.86) | 0.77 (0.29–2.05) |
APACC [36] | Recent history of sporadic colorectal adenomas | 272 | Placebo versus 160 mg aspirin per day versus 300 mg aspirin per day | 4.0 | Recurrent adenoma | 0.95 (0.75–1.21) | 0.91 (0.51–1.60) |
ukCAP [35] | Recent history of resected sporadic colorectal adenomas | 939 | Placebo versus 300 mg aspirin per day | 3.0 | Recurrent adenoma | 0.79 (0.63–0.99) | 0.63 (0.43–0.91) |
J-CAPP [38] | Recent history of resected colorectal adenomas and CRCs | 311 | Placebo versus 100 mg aspirin per day with or without folate supplement | 2.0 | Recurrent adenoma and CRC | 0.60 (0.36–0.98) | |
Chemoprevention of Colorectal Adenomas [39] | Recent history of resected sporadic colorectal adenomas | 1107 | Placebo versus 75 mg aspirin per day with 1,25-dihydroxycholecalciferol + calcium | 3.0 | Recurrent adenoma | 0.95 (0.61–1.48) | RR not reported |
seAFOod [40] | Recent history of resected sporadic colorectal adenomas | 709 | Placebo versus 2 g EPA-free fatty acid (FFA) per day or 300 mg aspirin per day or both treatments in combination | 1.0 | Recurrent adenoma | 0.99 (0.87 to 1.12) risk difference = –0.6% (95% CI, –8.5 to 7.2) p = 0.88 | RR not reported risk difference = −0.3% (95% CI, −4.1 to 3.5) |
Trial (Reference) | Study Population | Estimated Enrollement | Treatment Groups | Treatment Duration (Years) | Primary End Point | End Date |
---|---|---|---|---|---|---|
ABC trial [70] (NCT02927249) | Early stage node positive HER2 negative breast cancer patients | 2936 | Placebo versus Aspirin 300 mg per day | 5.0 | 5-years invasive disease-free survival | 2021 |
ASCOLT [71] (NCT00565708) | Dukes C or high-risk Dukes B colorectal cancer who have completed surgery and standard adjuvant chemotherapy | 1587 | Placebo versus Aspirin 200 mg per day | 5.0 | 5-years disease free survival | 2025 |
ASPIRED [73] (NCT02394769) | previously diagnosed with colorectal adenoma | 180 | Placebo versus Aspirin 81 or 325 mg per day | 12 weeks | Molecular biomarkers including urinary prostaglandin metabolites (PGE-M; primary endpoint), and specific biomarkers of colorectal carcinogenesis | 2029 |
ADD-ASPIRIN [72](NCT02804815) | Breast Cancer Prostate Cancer Colorectal Cancer Gastro-oesophageal Cancer | 11,000 | Placebo versus Aspirin 100 or 300 mg per day | 5.0 | 5- and 10-years overall survival 6-years invasive disease-free survival 6-years disease-free survival 5-years biochemical recurrence-free survival (bRFS) | 2026 |
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Frere, C.; Lejeune, M.; Kubicek, P.; Faille, D.; Marjanovic, Z.; the Groupe Francophone Thrombose et Cancer. Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies. Cancers 2019, 11, 1639. https://doi.org/10.3390/cancers11111639
Frere C, Lejeune M, Kubicek P, Faille D, Marjanovic Z, the Groupe Francophone Thrombose et Cancer. Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies. Cancers. 2019; 11(11):1639. https://doi.org/10.3390/cancers11111639
Chicago/Turabian StyleFrere, Corinne, Manon Lejeune, Pierre Kubicek, Dorothée Faille, Zora Marjanovic, and the Groupe Francophone Thrombose et Cancer. 2019. "Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies" Cancers 11, no. 11: 1639. https://doi.org/10.3390/cancers11111639