lenvatinib and Brain-Neoplasms

We describe the use of the tyrosine kinase inhibitor lenvatinib in a patient with brain tumor metastases from anaplastic thyroid carcinoma (ATC). A 52-year-old Japanese male presented with consciousness loss. Imaging revealed a thyroid tumor and multiple brain lesions. After the brain tumor's resection, pathology results provided the diagnosis of ATC. Total thyroidectomy was performed, followed by whole-brain irradiation. Additional brain lesions later developed, and lenvatinib therapy was initiated with no remarkable complications. However, the treatment effects were limited, and the patient died 2 months after starting lenvatinib, 202 days after the initial brain surgery. Relevant literature is discussed.

Topics: Antineoplastic Agents; Brain Neoplasms; Humans; Male; Middle Aged; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms

Anaplastic thyroid carcinoma (ATC) is a rare but aggressive undifferentiated tumor that frequently metastasizes to the brain. The multiple kinase inhibitor lenvatinib and sorafenib have been approved to treat unresectable differentiated thyroid cancer, and lenvatinib has been approved in Japan to treat ATC. This study compared the effects of lenvatinib and sorafenib in mouse models of central nervous system metastases of ATC. Immunodeficient mice were inoculated with ATC cells, and the effects of lenvatinib and sorafenib were evaluated in subcutaneous- and brain metastasis-mimicking models. Drug distribution was evaluated by imaging tandem mass spectrometry (ITMS). Neither lenvatinib nor sorafenib affected the viability of ATC cell lines, whereas both inhibited VEGF secretion by ATC cells. In the subcutaneous tumor model, both lenvatinib and sorafenib inhibited growth and were associated with reduced tumor microvessel density. In the brain metastasis-mimicking model, lenvatinib, but not sorafenib, inhibited the growth of ATC cells and reduced microvessel density in brain lesions. ITMS showed that lenvatinib was well-distributed in both subcutaneous and brain lesions, whereas the distribution of sorafenib was lower in brain than in subcutaneous lesions. These results demonstrate that lenvatinib is well-distributed in mouse models of ATC, and inhibited the growth of ATC brain lesions predominantly by inhibiting angiogenesis, suggesting that lenvatinib is highly potent against ATC brain metastases.

Topics: Angiogenesis Inhibitors; Animals; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Heterografts; Humans; Mice; Neoplasm Metastasis; Neovascularization, Pathologic; Phenylurea Compounds; Protein Kinase Inhibitors; Quinolines; Sorafenib; Thyroid Carcinoma, Anaplastic

Glioblastoma (GBM) is a lesion radiologically characterized by magnetic resonance imaging findings, such as ring enhancement with extensive perifocal edema and a butterfly appearance extending into the bilateral lobes. However, these characteristic findings could be changed by antiangiogenic therapy, with decreased contrast enhancement and improved perifocal edema. Herein, we report a case of GBM that arose during treatment with a tyrosine kinase inhibitor for another cancer.. A 57-year-old man presented with seizures. Until the seizure onset, he had been treated with the multireceptor tyrosine kinase inhibitor lenvatinib for 4 years for thyroid cancer and its metastasis to the thoracic vertebral body. Magnetic resonance imaging revealed a slightly high intensity lesion in the left frontal base area on T. Lenvatinib, which is antiangiogenic, might have affected the radiologic characteristics, as well as the pathology of the tumor. Brain tumors arising during treatment with receptor tyrosine kinases for other cancers could show atypical imaging findings.

Topics: Antineoplastic Agents; Brain Neoplasms; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Phenylurea Compounds; Protein Kinase Inhibitors; Quinolines; Thyroid Neoplasms; Treatment Outcome

Glioblastoma is the most aggressive primary brain tumor that originates from the glial cells in adults. Aberrant angiogenesis is essential for malignant glioblastoma tumorigenesis, development and metastasis. Lenvatinib is a multi‑targeted anticancer agent that targets of receptor tyrosine kinases including vascular endothelial growth factor receptor 1 and 2, fibroblast growth factor receptor 1, platelet‑derived growth factor receptor β and v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog. In the present study, the therapeutic effects of lenvatinib as a treatment for glioblastoma were investigated in vivo and in vitro. The maximum dose toxicity (MDT) and treatment‑associated adverse events of lenvatinib were identified by cytotoxicity assay in experimental mice. Increasing levels of the pro‑apoptosis genes caspase‑3, -8, -9 and -10 following lenvatinib treatment were determined by reverse transcription‑quantitative polymerase chain reaction, and apoptosis of the malignant gliomas cells was analyzed by FACS. In vivo treatment with lenvatinib for BV‑2 bearing male BALC/c nude mice was assessed via tumor growth suppression and long‑term observation of survival. Subsequent cytotoxic T lymphocyte responses were further analyzed to determine the in vivo efficacy of lenvatinib treatment in mice with glioblastoma. The MDT of lenvatinib was identified as 0.24 mg, with relatively few side effects and improved efficacy in mice. Lenvatinib (0.24 mg) significantly increased apoptosis in BV‑2, C6, BC3H1 and G422 glioma cell lines. Tumor growth was significantly inhibited and tumor‑bearing mice demonstrated an improved survival rate following treatment with lenvatinib. In conclusion, lenvatinib provided an effective treatment outcome, and the results of the present study may help to achieve a comprehensive therapeutic schedule for clinical application.

Topics: Animals; Apoptosis; Brain Neoplasms; Caspases; Cell Line, Tumor; Glioblastoma; Humans; Hypertension; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nausea; Neoplasm Staging; Phenylurea Compounds; Protein Kinase Inhibitors; Quinolines; RNA, Messenger; T-Lymphocytes, Cytotoxic; Transplantation, Heterologous