Clinical observation of apatinib‑related hypothyroidism in patients with advanced malignancies

Abstract

Thyroid dysfunction has been previously reported during treatment with certain small-molecule multi-tyrosine kinase inhibitors, including sunitinib and sorafenib. Apatinib, which has a similar mechanism of action to these inhibitors, has reportedly induced hypothyroidism during treatment. Fully elucidating drug-associated adverse events could aid in patient monitoring and recommendations of suitable management strategies. The current 2-year observational study monitored patients with solid tumors who were prescribed apatinib. A total of 149 patients treated with apatinib from February 2015 to January 2016 were included. Their thyroid function and thyroid ultrastructure was evaluated for at least 24 months or until death. The primary objective of the current study was evaluating accepted thyroid replacement treatment. Secondary objective was ultrastructural changes in the thyroid gland. The current study was approved by the Medical Ethics Committee of Qianfoshan Hospital, affiliated with Shandong University and written informed consent was obtained from all patients prior to commencing the clinical trial. A total of 53 (35.57%) patients developed hypothyroidism, which varied from subclinical (12 cases; 8.05%) to clinical (41 cases; 27.52%). Thyroid nodules were noted in 15 cases (10.07%). Furthermore, 3 cases (2.01%) had thyroid imaging reporting and data system scores of 4a/4b/4c and 12 cases (8.05%) had scores of 1, 2 and 3. A total of 25 patients (16.78%) experienced 1-2 grade fatigue and 2 patients (1.34%) reported 3-4 grade fatigue. There was no reported association between disease control rate and hypothyroidism. Apatinib significantly increased the risk of clinically relevant hypothyroidism and altered thyroid gland structure.

Editorial: Apatinib and Anlotinib in the Treatment of Radioactive Iodine Refractory and Highly Invasive Thyroid Carcinoma

“…Apatinib can selectively block VEGFR2 [ 11 ], suppressing the VEGF-stimulated migration and proliferation of vascular endothelial cells, reducing tumor microvessel density, and inhibiting tumor progression as well as metastasis [ 12 , 13 ]. Studies have confirmed the efficacy and safety of apatinib in treating malignancies with rich blood supply [ 14 ].…”