Gefitinib Induced Movement Disorder - A Case Report

Abstract

Background: Tyrosine kinase inhibitors targeting the Epidermal growth factor receptor have been used in the treatment of Non small cell lung cancer and Head and neck cancer. Gefitinib is a first generation tyrosine inhibitor associated with a relatively favourable toxicity profile (as compared to chemotherapy) and has been shown to be associated with the following rare but life threatening adverse effects – Interstitial lung disease, symptomatic prolongation of the corrected QT interval and severe elevation of transaminases, which may warrant discontinuation of drug. While, the use of EGFR tyrosine kinase inhibitors has been associated with an improvement in symptoms, in those with central nervous system involvement, the following case report is one of the first instances of a movement disorder bieng associated with the prolonged uninterrupted use of an EGFR tyrosine kinase inhibitor. Case details: A 57 year female, a known case of EGFR positive metastatic Adenocarcinoma of the lung with Pleural, liver and bone involvement, on Gefitinib 250 mg once daily since the past eight months, presented with complaints of involuntary movements involving the jaw and neck since the past 15 days. The movements interfered with activities of daily living and were not suppressed during sleep. She also reported bite marks on the lips and tongue along with mucosal ulcerations. These movements did not involve the upper or lower extremity. She did not complain of headache, vomiting, early morning nausea or blurring of vision. She had undergone ICD insertion for right sided pleural effusion and received palliative radiotherapy for vertebral metastasis (L1-L5). Response assessment CT was suggestive of significant interval change in the Lung mass with reduction in size and number of liver lesions. MRI Brain was not suggestive of any intracranial space occupying lesion. She was referred to the medical oncologist, where her EGFR Tyrosine kinase inhibitor was discontinued. She reported an improvement in her symptoms after the discontinuation of the Gefitinib. Discussion: A WHO-UMC category of possible/likely causation and score of 3 was obtained on Naranjo’s algorithm (possible adverse drug reaction) was established. Conclusion: Development of movement disorder might constitute an indication for discontinuation of Gefitinib therapy.