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Risk factor analysis for regorafenib-induced severe hypertension in metastatic colorectal cancer treatment

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Title: Risk factor analysis for regorafenib-induced severe hypertension in metastatic colorectal cancer treatment
Authors: Saito, Yoshitaka Browse this author →KAKEN DB
Takekuma, Yoh Browse this author →KAKEN DB
Komatsu, Yoshito Browse this author →KAKEN DB
Sugawara, Mitsuru Browse this author →KAKEN DB
Keywords: Regorafenib
Vascular endothelial growth factor (VEGF)
Pre-existing hypertension
Risk factor
Cardiovascular toxicity
Issue Date: 11-Oct-2022
Publisher: Springer
Journal Title: Supportive care in cancer
Volume: 30
Start Page: 10203
End Page: 10211
Publisher DOI: 10.1007/s00520-022-07381-z
Abstract: Regorafenib, a multikinase inhibitor, is effective in treating metastatic colorectal cancer (mCRC). Hypertension is a frequently occurring adverse effect caused by regorafenib regardless of previous treatment with vascular endothelial growth factor (VEGF) inhibitors in almost all patients. We identified the risk factors associated with regorafenib-induced severe hypertension. Patients with mCRC (n = 100) who received regorafenib were evaluated retrospectively. The primary endpoint was the evaluation of the risk factors for grade >= 3 hypertension. The association between pre-existing hypertension at baseline and grade >= 3 hypertension symptoms was also assessed. Patients with pre-existing hypertension at baseline accounted for 55% of the total patients. The starting doses of regorafenib were 160 mg (49.0% of patients), 120 mg (29.0%), and 80 mg (22.0%). The incidence of grade >= 3 hypertension was 30.0%. The median time to grade >= 3 symptom development was 7 days (range: 1-56 days). Additional antihypertensive treatment was administered to 83.6% of patients who developed hypertension. Logistic regression analyses revealed that baseline pre-existing hypertension complications and previous anti-VEGF treatment for >= 700 days were independent risk factors for grade >= 3 hypertension development. Further analyses revealed that pre-existing hypertension before anti-VEGF treatment (primary hypertension) was significantly related to the symptom development (adjusted odds ratio, 8.74; 95% confidence interval, 2.86-26.72; P = 0.0001). Our study suggests that pre-existing primary hypertension and previous anti-VEGF treatment for >= 700 days are independent risk factors for regorafenib-induced severe hypertension. Deeper understanding of the symptom nature and management can significantly contribute to safer interventions, necessitating further studies.
Rights: This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at:
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 齋藤 佳敬

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