Gastrointestinal perforation related to lenvatinib, an anti-angiogenic inhibitor that targets multiple receptor tyrosine kinases, in a patient with metastatic thyroid cancer

Lenvatinib, a novel potent multikinase inhibitor, was approved for the treatment of radioiodine-refractory differentiated thyroid cancer based on results from phase III trial (SELECT study). Thyroid cancer is a diverse disease that includes anaplastic thyroid cancer (ATC), which the most aggressive form of the disease, although it accounts for <2% of all thyroid cancers. Current treatments for ATC have limited efficacy. We report the case of a woman with recurrent well-differentiated papillary carcinoma of the thyroid that had transformed into ATC who developed a perforation of the small intestine secondary to a marked effect of lenvatinib. She received lenvatinib (24 mg once a day) at only two doses during two weeks due to pleurodesis with talc for malignant pleural effusion. Eventually, she developed peritonitis due to the perforation and died of sepsis. However, an autopsy revealed marked efficacy of lenvatinib for ATC at a metastatic site in the small intestine despite limited exposure to the drug. Here, we report on our experience with lenvatinib treatment and gastrointestinal perforation concerning anti-angiogenic therapy.