The Impact of Regorafenib on Cardiac Function in Metastatic Colorectal Cancer Patients a Retrospective Cohort Study
DOI:
https://doi.org/10.62497/IRABCS.2024.44Keywords:
Regorafenib, Metastatic colorectal cancer, Cardiac function, Cardiotoxicity, Retrospective cohort studyAbstract
Introduction: Metastatic colorectal cancer (mCRC) poses significant clinical challenges, necessitating the exploration of novel treatment modalities. Regorafenib, a multi-kinase inhibitor, has emerged as a promising therapeutic option for refractory mCRC. However, concerns regarding its potential cardiotoxic effects warrant comprehensive evaluation of its impact on cardiac function parameters in this patient population.
Methods: The purpose of this retrospective cohort research was to find out how regorafenib affected cardiac function measures in patients with metastatic colorectal cancer (mCRC) at the Pakistan Institute of Medical Sciences (PIMS) in Islamabad. 78 adult patients in all, having histologically proven mCRC, who were treated with regorafenib between January 2023 and March 2024 were included in the analysis. Baseline characteristics, treatment details, cardiac function parameters, and incidence of cardiac events were retrospectively analyzed. Statistical analyses were performed to assess changes in cardiac function parameters and identify predictors of cardiac toxicity associated with regorafenib therapy.
Results: Following regorafenib therapy, there was a significant decrease in left ventricular ejection fraction (LVEF), alterations in diastolic function indices, and an incidence of clinically significant cardiac events (12%), including heart failure, arrhythmias, and myocardial infarction. Subgroup analyses identified older age, male sex, pre-existing hypertension, longer treatment duration, and higher cumulative doses of regorafenib as potential predictors of cardiac toxicity.
Conclusion: This study underscores the potential cardiotoxic effects of regorafenib in mCRC patients and highlights the importance of personalized cardiac monitoring and risk management strategies during treatment. Further research is warranted to validate these findings and inform evidence-based approaches to optimize the cardiovascular safety of regorafenib in clinical practice.
Downloads
References
Aljubran A, Elshenawy MA, Kandil M, Zahir MN, Shaheen A, Gad A, Alshaer O, Alzahrani A, Eldali A, Bazarbashi S. Efficacy of regorafenib in metastatic colorectal cancer: a multi-institutional retrospective study. Clinical Medicine Insights: Oncology. 2019 Jan;13:1179554918825447.
Giampieri R, Prete MD, Prochilo T, Puzzoni M, Pusceddu V, Pani F, Maccaroni E, Mascia R, Baleani MG, Meletani T, Berardi R. Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis. Scientific Reports. 2017 Apr 5;7(1):45703.
Nakashima M, Li K, Chen Q, de Silva S, Li H, Kawakami K, Wei Q, Luo S, Zhao H. Appropriate dose of regorafenib based on body weight of colorectal cancer patients: a retrospective cohort study. BMC cancer. 2023 Dec 21;23(1):1268.
Keramida K, Charalampopoulos G, Filippiadis D, Tsougos E, Farmakis D. Cardiovascular complications of metastatic colorectal cancer treatment. Journal of Gastrointestinal Oncology. 2019 Aug;10(4):797.
Calcagno F, Lenoble S, Lakkis Z, Nguyen T, Limat S, Borg C, Jary M, Kim S, Nerich V. Efficacy, safety and cost of regorafenib in patients with metastatic colorectal cancer in French clinical practice. Clinical Medicine Insights: Oncology. 2016 Jan;10:CMO-S38335.
Ottaiano A, Santorsola M, Perri F, Granata V, Cascella M, Sabbatino F, Nasti G. Survival and Toxicities of Metastatic Colorectal Cancer Patients Treated with Regorafenib before TAS-102 or Vice Versa: A Mono-Institutional Real-Practice Study. Journal of Clinical Medicine. 2023 Jan 11;12(2):596.
Van Cutsem E, Martinelli E, Cascinu S, Sobrero A, Banzi M, Seitz JF, Barone C, Ychou M, Peeters M, Brenner B, Hofheinz RD. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: results of the large, single‐arm, open‐label phase IIIb CONSIGN study. The oncologist. 2019 Feb 1;24(2):185-92.
Yekedüz E, Aktaş EG, Köksoy EB, Doğan N, Ürün Y, Utkan G. The prognostic role of polypharmacy in metastatic colorectal cancer patients treated with regorafenib. Future Oncology. 2022 Mar;18(9):1067-76.
Huemer F, Piringer G, Schlintl V, Hackl H, Rinnerthaler G, Thaler J, Greil R, Weiss L. Hospitalizations and clinical outcome in metastatic colorectal cancer during regorafenib or TAS-102 therapy. Cancers. 2020 Sep 30;12(10):2812.
Bekaii-Saab, T.S., Ou, F.S., Ahn, D.H., Boland, P.M., Ciombor, K.K., Heying, E.N., Dockter, T.J., Jacobs, N.L., Pasche, B.C., Cleary, J.M. and Meyers, J.P., 2019. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. The lancet oncology, 20(8), pp.1070-1082.
Hatori M, Kawakami K, Wakatsuki T, Shinozaki E, Kobayashi K, Aoyama T, Nakano Y, Suzuki K, Yamaguchi K, Hama T. Association Between Regorafenib Dose and Efficacy Against Metastatic Colorectal Cancer in a Real-World Setting. Dose-Response. 2021 Oct 4;19(4):15593258211047658.
Karakurt Eryılmaz, M., Kerimoğlu, Ü., Karaağaç, M., Yalçın Müsri, F., Araz, M. and Artaç, M., 2021. Small bowel wall edema induced by regorafenib is associated with regorafenib intolerance and shorter survival in patients with metastatic colorectal cancer: A retrospective study. Journal of Oncology Pharmacy Practice, 27(8), pp.1929-1935.
Saito Y, Takekuma Y, Komatsu Y, Sugawara M. Risk factor analysis for regorafenib-induced severe hypertension in metastatic colorectal cancer treatment. Supportive care in cancer. 2022 Dec;30(12):10203-11.
Xie G, Gong Y, Wu S, Li C, Yu S, Wang Z, Chen J, Zhao Q, Li J, Liang H. Meta-analysis of regorafenib-associated adverse events and their management in colorectal and gastrointestinal stromal cancers. Advances in Therapy. 2019 Aug 1;36:1986-98.
García-Alfonso P, Feliú J, García-Carbonero R, Grávalos C, Guillén-Ponce C, Sastre J, García-Foncillas J. Is regorafenib providing clinically meaningful benefits to pretreated patients with metastatic colorectal cancer?. Clinical and Translational Oncology. 2016 Nov;18:1072-81.
Zhou YW, Wang JL, Li QF, He YL, Li LJ, Liu RZ, Chen Y, Zhang S, Qiu M, Liu JY. Efficacy and safety of raltitrexed plus S-1 versus regorafenib in patients with refractory metastatic colorectal cancer: a real-world propensity score matching study. Therapeutic Advances in Gastroenterology. 2022 May;15:17562848221098246.
Del Prete S, Cennamo G, Leo L, Montella L, Vincenzi B, Biglietto M, Andreozzi F, Prudente A, Iodice P, Savastano C, Nappi A. Adherence and safety of regorafenib for patients with metastatic colorectal cancer: observational real-life study. Future Oncology. 2017 Feb;13(5):415-23.
Xu X, Yu Y, Liu M, Liang L, Liu T. Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review. Translational Cancer Research. 2022 Jan;11(1):276.
Ramaswamy A, Ostwal V, Pande N, Sharma A, Patil S, Thippeswamy R, Ghadyalpatil N, Roy R, Peshwe H, Poladia B, Rajamanickam D. Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the Regorafenib in metastatic colorectal cancer-an Indian Exploratory analysis study. South Asian journal of cancer. 2019 Jan;8(01):22-6.
Petrioli R, Chirra M, Messuti L, Fiaschi AI, Savelli V, Martellucci I, Francini E. Efficacy and safety of regorafenib with 2/1 schedule for patients≥ 75 years with metastatic colorectal cancer (mCRC) after failure of 2 lines of chemotherapy. Clinical Colorectal Cancer. 2018 Dec 1;17(4):307-12.
Majithia N, Grothey A. Regorafenib in the treatment of colorectal cancer. Expert opinion on pharmacotherapy. 2016 Jan 2;17(1):137-45.
de la Fouchardière C. Regorafenib in the treatment of metastatic colorectal cancer. Future Oncology. 2018 Sep;14(22):2239-46.
Conti M, Bolzacchini E, Luchena G, Bertu’ L, Tagliabue P, Aglione S, Ardizzoia A, Arnoffi J, Guida FM, Bertolini A, Pastorini A. Tas-102 for refractory metastatic colorectal cancer: a multicenter retrospective cohort study. Cancers. 2023 Jul 2;15(13):3465.
Downloads
Published
Issue
Section
Categories
License
Copyright (c) 2024 Muhammad Rizwan , Muhammad Hamza Yousuf, Shafiq Ur Rahman, Rizwan Ali, Eisha Turazia Tahir, Rabbia Pasha (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Authors retain copyright to their work published in the IRABCS journal under the Creative Commons Attribution Non-Commercial No Derivatives License (CC BY-NC-ND 4.0).