Cancer Therapy-Induced Cardiotoxicity: Results of the Analysis of the UK DEFINE Database
Simple Summary
Abstract
1. Introduction
2. Methods
- Chemotherapy: carboplatin, cisplatin, cyclophosphamide, docetaxel, doxorubicin, epirubicin, gemcitabine, methotrexate, paclitaxel, pemetrexed, vincristine, vinorelbine;
- Targeted therapy: afatinib, bevacizumab, erlotinib, gefitinib, nintedanib, osimertinib;
- Immunotherapy: atezolizumab, pembrolizumab.
NSCLC Drugs | Number of Patients with C34 Diagnosis and Drug Use |
---|---|
Carboplatin | 20991 |
Cisplatin | 8308 |
Pemetrexed | 7839 |
Etoposide | 7199 |
Gemcitabine | 7015 |
Vinorelbine | 6336 |
Pembrolizumab | 3332 |
Docetaxel | 2403 |
Erlotinib | 2271 |
Cyclophosphamide | 1657 |
Methotrexate | 1359 |
Doxorubicin | 1212 |
Vincristine | 1120 |
Paclitaxel | 1110 |
Atezolizumab | 995 |
Gefitinib | 752 |
Nintedanib | 574 |
Afatinib | 570 |
Celecoxib | 488 |
Epirubicin | 401 |
Topotecan | 367 |
Osimertinib | 345 |
Irinotecan | 329 |
Bevacizumab | 310 |
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Alteplase | Amiodarone | Amlodipine | Apixaban | Atenolol | Bisoprolol | Candesartan | Diltiazem | Doxazosin | Epinephrine | Lidocaine | Lisinopril | Losartan | Ramipril | Rivaroxaban | Streptokinase | Tenecteplase | Verapamil | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Afatinib | −0.061 | 0.206 | −0.372 ** | −0.565 *** | 0.354 ** | −0.195 | −0.357 ** | 0.279 * | −0.331 ** | −0.407 *** | 0.271 * | 0.147 | −0.322 ** | −0.146 | −0.341 ** | 0.233 | 0.308 * | 0.345 ** |
Atezolizumab | 0.495 *** | −0.380 ** | 0.545 *** | 0.955 *** | −0.781 *** | 0.312 * | 0.500 *** | −0.435 *** | 0.594 *** | 0.242 | −0.185 | −0.430 *** | 0.339 ** | 0.062 | 0.425 *** | −0.247 * | −0.222 | −0.596 *** |
Bevacizumab | 0.329 ** | 0.039 | 0.692 *** | 0.773 *** | −0.362 ** | 0.561 *** | 0.611 *** | −0.082 | 0.674 *** | 0.524 *** | −0.192 | 0.027 | 0.572 *** | 0.423 *** | 0.588 *** | −0.076 | −0.253 * | −0.217 |
Carboplatin | 0.275 * | 0.366 ** | 0.775 *** | 0.549 *** | 0.004 | 0.725 *** | 0.713 *** | 0.311 * | 0.753 *** | 0.530 *** | 0.196 | 0.400 ** | 0.721 *** | 0.645 *** | 0.820 *** | 0.056 | −0.136 | 0.200 |
Cisplatin | −0.295 * | 0.648 *** | 0.175 | −0.394 ** | 0.741 *** | 0.326 ** | 0.156 | 0.713 *** | 0.129 | 0.256 * | 0.237 | 0.747 *** | 0.321 ** | 0.509 *** | 0.299 * | 0.248 * | 0.050 | 0.657 *** |
Cyclophosphamide | −0.034 | 0.623 *** | 0.483 *** | 0.026 | 0.416 *** | 0.580 *** | 0.450 *** | 0.533 *** | 0.481 *** | 0.320 ** | 0.107 | 0.600 *** | 0.571 *** | 0.631 *** | 0.488 *** | 0.224 | 0.071 | 0.483 *** |
Docetaxel | −0.393 ** | 0.783 *** | 0.172 | −0.425 *** | 0.786 *** | 0.450 *** | 0.226 | 0.876 *** | 0.158 | 0.159 | 0.196 | 0.806 *** | 0.351 ** | 0.569 *** | 0.282 * | 0.451 *** | 0.130 | 0.883 *** |
Doxorubicin | 0.359 ** | 0.330 ** | 0.583 *** | 0.334 ** | 0.091 | 0.460 *** | 0.436 *** | 0.084 | 0.490 *** | 0.380 ** | 0.189 | 0.305 * | 0.541 *** | 0.466 *** | 0.517 *** | −0.133 | 0.023 | 0.093 |
Epirubicin | −0.346 ** | 0.769 *** | 0.211 | −0.411 *** | 0.785 *** | 0.418 *** | 0.209 | 0.767 *** | 0.136 | 0.327 ** | 0.153 | 0.809 *** | 0.354 ** | 0.616 *** | 0.369 ** | 0.383 ** | 0.152 | 0.836 *** |
Erlotinib | −0.449 *** | 0.497 *** | −0.425 *** | −0.896 *** | 0.808 *** | −0.179 | −0.394 ** | 0.537 *** | −0.466 *** | −0.195 | 0.209 | 0.521 *** | −0.228 | 0.050 | −0.310 * | 0.297 * | 0.273 * | 0.674 *** |
Gefitinib | 0.551 *** | −0.423 *** | −0.091 | 0.193 | −0.409 *** | −0.257 * | −0.233 | −0.627 *** | −0.098 | −0.162 | 0.003 | −0.447 *** | −0.249 * | −0.329 ** | −0.240 | −0.377 ** | 0.179 | −0.491 *** |
Gemcitabine | 0.288 * | −0.149 | 0.493 *** | 0.609 *** | −0.387 ** | 0.296 * | 0.410 *** | −0.273 * | 0.477 *** | 0.247 * | −0.011 | −0.111 | 0.371 ** | 0.219 | 0.424 *** | −0.246 | −0.189 | −0.366 ** |
Methotrexate | 0.039 | 0.175 | 0.085 | −0.123 | 0.332 ** | 0.132 | 0.077 | 0.132 | 0.031 | 0.013 | 0.041 | 0.321 ** | 0.138 | 0.205 | 0.145 | 0.003 | 0.061 | 0.281 * |
Nintedanib | 0.434 *** | −0.268 * | 0.512 *** | 0.818 *** | −0.641 *** | 0.330** | 0.451 *** | −0.327 ** | 0.548 *** | 0.198 | −0.210 | −0.332 ** | 0.355 ** | 0.094 | 0.338 ** | −0.245 | −0.191 | −0.478 *** |
Osimertinib | 0.407 *** | −0.298 * | 0.572 *** | 0.906 *** | −0.666 *** | 0.340 ** | 0.510 *** | −0.408 *** | 0.575 *** | 0.386 ** | −0.256 * | −0.321 ** | 0.398 ** | 0.145 | 0.447 *** | −0.235 | −0.248 * | −0.536 |
Paclitaxel | 0.466 *** | −0.242 | 0.584 *** | 0.843 *** | −0.570 *** | 0.397 ** | 0.514 *** | −0.270 * | 0.596 *** | 0.346 ** | −0.125 | −0.233 | 0.390 ** | 0.195 | 0.455 *** | −0.187 | −0.229 | −0.471 *** |
Pembrolizumab | 0.500 *** | −0.433 *** | 0.454 *** | 0.879 *** | −0.759 *** | 0.224 | 0.380 ** | −0.471 *** | 0.494 *** | 0.123 | −0.206 | −0.485 *** | 0.217 | −0.026 | 0.320 * | −0.290 * | −0.194 | −0.635 *** |
Pemetrexed | −0.141 | 0.181 | 0.128 | 0.011 | 0.082 | 0.133 | 0.091 | 0.061 | 0.069 | 0.224 | −0.153 | 0.163 | 0.127 | 0.233 | 0.131 | −0.007 | −0.129 | 0.106 |
Vincristine | 0.499 *** | −0.468 *** | 0.332 ** | 0.744 *** | −0.708 *** | 0.106 | 0.193 | −0.541 *** | 0.342 ** | 0.151 | −0.159 | −0.488 *** | 0.090 | −0.091 | 0.205 | −0.372 ** | −0.195 | −0.607 *** |
Vinorelbine | −0.452 *** | 0.760 *** | 0.189 | −0.409 *** | 0.779 *** | 0.401 ** | 0.241 | 0.825 *** | 0.156 | 0.177 | 0.175 | 0.780 *** | 0.383 ** | 0.545 *** | 0.310 * | 0.358 ** | 0.075 | 0.786 *** |
Oncology Drug | Cardiology Drug That Was Most Associated with Each Oncology Drug | Cardiovascular Disease(s) That the Corresponding Cardiology Drug Was Assumed to Treat |
---|---|---|
Afatinib | Atenolol | Ischaemia/hypertension |
Atezolizumab | Apixaban | Atrial fibrillation |
Bevacizumab | Apixaban | Atrial fibrillation |
Carboplatin | Rivaroxaban | Arterial/venous thromboembolic event |
Cisplatin | Lisinopril | Hypertension/cardiac failure/arrest |
Cyclophosphamide | Ramipril | Hypertension/cardiac failure/arrest |
Docetaxel | Verapamil | Arrhythmia/hypertension |
Doxorubicin | Amlodipine | Hypertension |
Epirubicin | Verapamil | Arrhythmia/hypertension |
Erlotinib | Atenolol | Ischaemia/hypertension |
Gefitinib | Alteplase | Myocardial infarction |
Gemcitabine | Apixaban | Atrial fibrillation |
Methotrexate | Atenolol | Ischaemia/hypertension |
Nintedanib | Apixaban | Atrial fibrillation |
Osimertinib | Apixaban | Atrial fibrillation |
Paclitaxel | Apixaban | Atrial fibrillation |
Pembrolizumab | Apixaban | Atrial fibrillation |
Pemetrexed | Ramipril | Hypertension/cardiac failure/arrest |
Vincristine | Apixaban | Atrial fibrillation |
Vinorelbine | Diltiazem | Hypertension |
Drug–Drug Pair | Linear Regression Analysis | |||
---|---|---|---|---|
NSCLC Drug | Cardiotoxicity Drug | Coefficient | Intercept | R2 Value |
Atezolizumab | Apixaban | 1.337 | 4949.882 | 0.911 |
Osimertinib | Apixaban | 1.204 | 5265.088 | 0.820 |
Erlotinib | Apixaban | −4.095 | 9610.698 | 0.802 |
Docetaxel | Verapamil | 5.540 | 1848.673 | 0.779 |
Pembrolizumab | Apixaban | 2.595 | 3926.500 | 0.773 |
Docetaxel | Diltiazem | 1.661 | −215.759 | 0.767 |
Paclitaxel | Apixaban | 0.002 | 4595.091 | 0.711 |
Epirubicin | Verapamil | 8.916 | 1077.783 | 0.699 |
Vinorelbine | Diltiazem | 7.615 | −248.661 | 0.681 |
Carboplatin | Rivaroxaban | 82.480 | 221,044.146 | 0.672 |
Nintedanib | Apixaban | 0.316 | 1242.011 | 0.669 |
Epirubicin | Lisinopril | 171.813 | 100,349.747 | 0.655 |
Erlotinib | Atenolol | 3.340 | 5815.185 | 0.653 |
Docetaxel | Lisinopril | 100.603 | 120,115.002 | 0.649 |
Vinorelbine | Verapamil | 23.997 | 1988.937 | 0.618 |
Docetaxel | Atenolol | 7.436 | 2241.347 | 0.618 |
Epirubicin | Atenolol | 12.625 | 823.243 | 0.616 |
Docetaxel | Amiodarone | 19.449 | 19,261.962 | 0.614 |
Atezolizumab | Atenolol | −0.990 | 9483.021 | 0.610 |
Vinorelbine | Lisinopril | 473.929 | 115,861.880 | 0.609 |
Vinorelbine | Atenolol | 35.861 | 1778.631 | 0.607 |
Carboplatin | Amlodipine | 0.908 | 2562.594 | 0.600 |
Bevacizumab | Apixaban | 5.869 | 1829.886 | 0.597 |
Epirubicin | Amiodarone | 32.446 | 15,888.632 | 0.591 |
Epirubicin | Diltiazem | 2.474 | −330.944 | 0.589 |
Vinorelbine | Amiodarone | 91.768 | 18,413.891 | 0.577 |
Pembrolizumab | Atenolol | −2.024 | 10,352.082 | 0.575 |
Carboplatin | Doxazosin | 0.168 | 483.829 | 0.567 |
Cisplatin | Lisinopril | 109.250 | 140,300.077 | 0.558 |
Vincristine | Apixaban | 170.599 | 4044.368 | 0.553 |
Cisplatin | Atenolol | 8.214 | 3656.904 | 0.549 |
Carboplatin | Bisoprolol | 0.814 | 2592.982 | 0.525 |
Carboplatin | Losartan | 1.534 | 6331.187 | 0.519 |
Carboplatin | Candesartan | 0.199 | 797.088 | 0.508 |
Cisplatin | Diltiazem | 1.583 | 238.578 | 0.508 |
Vincristine | Atenolol | −146.874 | 10,476.737 | 0.501 |
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Chan, S.H.Y.; Fitzpatrick, R.W.; Layton, D.; Webley, S.; Salek, S. Cancer Therapy-Induced Cardiotoxicity: Results of the Analysis of the UK DEFINE Database. Cancers 2025, 17, 311. https://doi.org/10.3390/cancers17020311
Chan SHY, Fitzpatrick RW, Layton D, Webley S, Salek S. Cancer Therapy-Induced Cardiotoxicity: Results of the Analysis of the UK DEFINE Database. Cancers. 2025; 17(2):311. https://doi.org/10.3390/cancers17020311
Chicago/Turabian StyleChan, Stefanie Ho Yi, Raymond W. Fitzpatrick, Deborah Layton, Sherael Webley, and Sam Salek. 2025. "Cancer Therapy-Induced Cardiotoxicity: Results of the Analysis of the UK DEFINE Database" Cancers 17, no. 2: 311. https://doi.org/10.3390/cancers17020311
APA StyleChan, S. H. Y., Fitzpatrick, R. W., Layton, D., Webley, S., & Salek, S. (2025). Cancer Therapy-Induced Cardiotoxicity: Results of the Analysis of the UK DEFINE Database. Cancers, 17(2), 311. https://doi.org/10.3390/cancers17020311