lenvatinib and Hypothyroidism

Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used for the treatment of various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events, especially hypothyroidism. This study investigated the incidence of hypothyroidism due to LEN and the relationships between hypothyroidism incidence and patient demographics by analyzing clinical laboratory data from HCC patients treated with LEN.. This was a single-center, retrospective study of HCC patients who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration.. In total, 61 patients with HCC were enrolled. High-grade hypothyroidism (CTCAE Grade 2-3) was found in 36.1% (22/61 patients). In high-grade hypothyroidism, eosinophil (EOSINO) count was significantly low (p = 0.029). The cutoff value of EOSINO count was estimated to be approximately 150/µL. The adjusted odds ratios of high-grade hypothyroidism for current smoking and EOSINO count <150/µL were 0.237 (95% confidence interval: 0.063-0.893) and 4.219 (95% confidence interval: 1.119-15.92), respectively.. The results showed that noncurrent smoking and EOSINO count <150/µL are risk factors for LEN-induced high-grade hypothyroidism.

Topics: Carcinoma, Hepatocellular; Humans; Hypothyroidism; Liver Neoplasms; Retrospective Studies; Risk Factors

Hypothyroidism is a common adverse event of lenvatinib therapy for hepatocellular carcinoma (HCC), whereas thyrotoxicosis has rarely been reported in clinical trials. A 74-year-old man complaining of abdominal pain was found to have liver tumors and paraaortic lymphadenopathy. The intrahepatic lesions were diagnosed as HCC by angiography and treated with transcatheter arterial chemoembolization. Although localized prostate cancer was discovered incidentally, the etiology of paraaortic lymphadenopathy was assumed to be metastatic HCC. Lenvatinib 12 mg/day was started when his thyroid function tests were almost normal but was interrupted because of thyrotoxicosis. The patient was negative for tested thyroid autoantibodies. Color Doppler ultrasonography detected reduced thyroid blood flow, suggesting destructive thyroiditis. Although he resumed lenvatinib at 8 mg/day once his serum level of free thyroxine normalized, thyrotoxicosis recurred. Subsequently, he suffered hypothyroidism, which exacerbated despite levothyroxine replacement. Lenvatinib was discontinued as it was ineffective against the paraaortic lymph node metastasis, and external-beam radiotherapy was performed. After the completion of radiotherapy, the thyroid dysfunction significantly improved. In summary, lenvatinib for HCC can induce transient thyrotoxicosis followed by hypothyroidism, which is compatible with destructive thyroiditis. During lenvatinib therapy, close monitoring of thyroid function and appropriate management of thyrotoxicosis as well as hypothyroidism are essential.

Topics: Aged; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Humans; Hypothyroidism; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Phenylurea Compounds; Quinolines; Thyroiditis; Thyrotoxicosis

Lenvatinib has anti-tumor activity against advanced hepatocellular carcinoma (HCC). Hypothyroidism is also a frequent complication in patients treated with lenvatinib. However, studies on lenvatinib-induced thyroid toxicity and destructive thyroiditis are limited. Therefore, this study aimed to clarify the frequency and timing of thyroid abnormalities in lenvatinib for unresectable HCC. This retrospective study enrolled 50 patients with advanced HCC treated with lenvatinib. Patients were classified to have euthyroid, subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis. The timing of thyroid dysfunction was assessed, and risk factors for incident hypothyroidism or thyrotoxicosis were evaluated using multivariate models. Subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis occurred in 7 (14.0%), 26 (52.0%), and 5 (10.0%) patients, respectively. In the 33 patients with hypothyroidism, 27 (84.4%) developed the condition within 2 weeks of starting lenvatinib treatment. Of the 5 patients with thyrotoxicosis, 3 developed the condition within 8 weeks of starting lenvatinib administration. One patient developed thyrotoxicosis in only 1 week of the initiation of treatment. No correlation between the presence of antibodies and the incidence and severity of thyroid dysfunction due to the autoimmune mechanism was observed. The progression-free survival was significantly better in the hypothyroidism group. Lenvatinib treatment for unresectable HCC not only causes hypothyroidism, but also thyrotoxicosis. Moreover, these thyroid conditions develop within the early period of treatment at a higher prevalence. Patients with thyroid dysfunction had better prognosis. Based on these results, in patients administered with lenvatinib, there is need for careful assessment for the possibility of thyroid dysfunction from the onset of treatment.

Topics: Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Female; Follow-Up Studies; Humans; Hypothyroidism; Incidence; Japan; Liver Neoplasms; Male; Middle Aged; Phenylurea Compounds; Quinolines; Retrospective Studies; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroiditis; Thyrotoxicosis