Adverse Side Effects of Crizotinib in the Treatment of Anaplastic Lymphoma Kinase-Mutated Non-small Cell Lung Cancer: A Systematic Review

Abstract

Lung cancer is the leading cause of cancer deaths worldwide, with the majority consisting of non-small cell lung cancer (NSCLC). Genetic mutations present an opportunity for targeted therapy, in addition to current mainstay treatments such as chemotherapy and radiotherapy. Overall, 5% of NSCLCs have an anaplastic lymphoma kinase (ALK) mutation, often prevalent in a younger population. Crizotinib is an ALK inhibitor that was approved to treat ALK-mutated advanced NSCLC. While common side effects such as nausea, fatigue, and diarrhea are mostly well tolerated, adverse side effects can lead to treatment discontinuation or adjustment or can be fatal. This systematic review used articles searched on Google Scholar and PubMed which were assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa Scale. This yielded nine papers consisting of randomized controlled trials and cohort studies. Side effects resulting in cessation of treatment or dose reduction included liver dysfunction, nausea, neutropenia, and QT prolongation. This review showed that crizotinib has a better side effect profile than chemotherapy in ALK-positive NSCLC, even though toxicities leading to treatment withdrawal are present. Adverse effects were tackled by dose reduction, temporary withdrawal from treatment, and close monitoring.