Esophagitis resulting from treatment with crizotinib for anaplastic lymphoma kinase rearrangement-positive lung adenocarcinoma: A case report

Abstract

Abstract. Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed type of cancer and is a leading cause of cancer-related mortality worldwide. Treatment is currently focused on individualization according to the molecular profile of the disease. Here we present the case of a 41-year-old patient who presented with multiple pulmonary nodules, a left pleural effusion and an ovarian tumor. Adenocarcinoma of the lung was diagnosed from pathological examination of the pleural effusion and the surgically resected ovarian tumor, and chemotherapy was initiated. Relapse was experienced following third-line chemotherapy with pemetrexed and anaplastic lymphoma kinase (ALK)-positive adenocarcinoma was diagnosed using a specimen from the resected ovarian tumor. Subsequently, crizotinib therapy was initiated. Eight days later the patient developed severe nausea and vomiting and esophagitis was diagnosed by gastrointestinal endoscopic examination. Following the interruption of crizotinib treatment by treatment with a proton pump inhibitor (PPI), crizotinib treatment was re-initiated and was effective for a minimum of 6 months. Clinicians should be aware that treatment with crizotinib may result in severe esophagitis. IntroductionNon-small-cell lung cancer (NSCLC) is the most commonly diagnosed type of cancer and is a leading cause of cancer-related mortality worldwide (1). Currently, strategies aiming to maximize treatment benefit for NSCLC are centered on individualized treatments based on the molecular profile of the disease. The identification of mutations of the epidermal growth factor receptor (EGFR) gene and development of its tyrosine kinase inhibitors have signifficantly affected the potency of the response to NSCLC treatment and has led to additional oncogenic drivers being aggressively investigated.Anaplastic lymphoma kinase (ALK) rearrangements in NSCLC were first described in 2007 (2). Several ALK inhibitors have been introduced in clinical trials or are currently under preclinical development. Among these, crizotinib was shown to possess marked therapeutic efficacy (3) and was approved by the US Food and Drug Administration (FDA) in 2011, shortly after its development.Crizotinib is used worldwide for the treatment of ALK-positive NSCLC; however, there is increasing accumulation of data with regard to its potential adverse events, which may be severe. Here we present the case report of a patient with ALK-positive NSCLC and severe esophagitis caused by crizotinib treatment. Case reportA 41-year-old woman was admitted to our hospital with a left pleural effusion. Adenocarcinoma cells were detected by cytological examination of the pleural effusion. Whole-body computed tomography (CT) revealed multiple nodular shadows in the left pulmonary field, a left pleural effusion and a multilocular tumor in the right ovary (Fig. 1A and B). The ovarian tumor was surgically resected and immunohistochemistry (IHC) revealed characteristics of a primary lung adenocarcinoma. Active EGFR mutations were not identified. This st...

Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma

“…The major adverse effects of crizotinib are vision disorder, diarrhea, nausea, and vomiting. In addition, several reports have demonstrated that severe esophagitis may be induced by crizotinib (8)(9)(10)(11)(12)(13). Here, we report a case of recurrent esophagitis induced by crizotinib that was successfully managed by the alternate-day administration of crizotinib.…”

“…To our knowledge, there are six case reports of crizotinib-induced esophagitis (8)(9)(10)(11)(12)(13). The mechanism of crizotinib-induced esophagitis is not clear.…”

ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma

“…Although there have been some previous case reports of the efficacy of ALK -tyrosine kinase inhibitor (TKI) therapy in patients in whom ALK protein expression was detected in MPE samples (31,32), we obtained efficacy data with crizotinib in a total of 11 lung adenocarcinoma patients who were Ventana IHC ALK (D5F3)-positive. Two patients had CR (2/11, 18.2%), 5 had PR (5/11, 45.5%), and 3 had SD (3/11, 27.3%).…”

Severe contact esophagitis in a patient taking crizotinib: A case report

“…Since its approval, there have been five cases of esophagitis reported in patients taking crizotinib, which have been attributed to “pill esophagitis” in two cases and unknown causes in the other three cases . In three of these cases, crizotinib was not recommenced or was recommenced, and maintained, at a lower dose.…”