Tohoku J. Exp. Med., 2021 July, 254(3)

Intestinal Perforation in a Patient with Colon Cancer during Treatment with Regorafenib: A Case Report and Review of the Literature

Ryusuke Ouchi,1,2 Kouji Okada,1,2 Kensuke Usui,1,2 Naoko Kurata,2 Shinju Suzuki,3 Munenori Nagao,3 Yoshiteru Watanabe1,2 and Kaori Koyama3

1Division of Clinical Pharmaceutics and Pharmacy Practice, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan
2Department of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan
3Department of Supportive Medicine and Care for Cancer, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan

The multikinase inhibitor, regorafenib, is known to exert its antitumor effects by targeting several kinases, inhibiting interstitial intracellular signaling and suppressing tumor cell proliferation. Regorafenib causes gastrointestinal perforation and gastrointestinal fistula as adverse events, and discontinuation is recommended if these adverse events occur during administration. However, there are no prescribed standards for re-administration after discontinuation and for administration in patients with a history of gastrointestinal perforation. Herein, we report a case of gastrointestinal perforation in a patient, with a history of gastrointestinal microperforation, undergoing bevacizumab therapy, within a few days of starting regorafenib; this had a significant effect on the prognosis. The site of gastrointestinal perforation was consistent with previously reported sites around the tumor and at the anastomotic site. Based on a review of literature and our experience with the case presented here, we recommend that administration of regorafenib to patients with a history of gastrointestinal perforation should be avoided to the extent possible. Moreover, in case of prior administration of a drug reported to cause gastrointestinal perforation, such as an anti-VEGFR drug, the risk of gastrointestinal perforation should be considered during the administration of regorafenib. In the event of complaints, such as abdominal pain, gastrointestinal perforation should be considered as a differential diagnosis and appropriate tests and treatments should be initiated at an early stage.

Key words —— anti-VEGFR drug; bevacizumab; colon cancer; intestinal perforation; regorafenib

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Tohoku J. Exp. Med 2021, 254, 207-211.

Correspondence: Ryusuke Ouchi, Division of Clinical Pharmaceutics and Pharmacy Practice, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi 983-8536, Japan.

e-mail: rouchi@tohoku-mpu.ac.jp