Crizotinib-induced esophagitis developing during the course of treatment for adenocarcinoma of the lungs associated with the EML4/ALK fusion gene

Abstract

Background. Crizotinib became available for the treatment of lung cancer associated with the ALK fusion gene in Japan in March 2012. However, the causal association between the administration of crizotinib and rare side effects remains unclear. Case. A 43-year-old woman with lung adenocarcinoma associated with EML4/ ALK gene translocation (cT4N3M1b: Stage IV) received second-line chemotherapy consisting of one 250-mg crizotinib capsule twice daily. She experienced nausea and vomited several hours after crizotinib administration on day 1 and subsequently suffered from severe esophagalgia causing significant dietary intake reduction on day 2. Ultimately, she developed severe esophagitis, and the crizotinib therapy was temporally discontinued on day 4. Her symptoms improved shortly thereafter, although they again appeared following the readministration of crizotinib, even under a reduced dose (one 200-mg capsule twice daily), thus leading to crizotinib termination on day 7. Positron emission tomography conducted during the washout period showed the circumferential uptake of fluorodeoxyglucose in the middle and lower esophagus. In addition, esophagogastroduodenoscopy revealed significant inflammation in the esophageal mucosa. Collectively, the patient was diagnosed with crizotinib-induced esophagitis, as the series of recurrent episodes of esophageal pain appeared to be due to the administration of crizotinib. After recovering from all esophagitis-related symptoms, the patient again began to take 200 mg of crizotinib daily under close monitoring of her symptoms. She has continuously received crizotinib for seven months, and the pulmonary target lesions have continued to exhibit "stable disease". Conclusions. Although acute esophagitis is rarely reported as a side effect of crizotinib therapy, the clinical manifestations of this case suggest a strong cause and effect relationship. © 2014 The Japan Lung Cancer Society.