crizotinib and Esophagitis

Crizotinib is an oral tyrosine kinase inhibitor, approved by the FDA in 2011, for use in anaplastic lymphoma kinase positive, metastatic, non-small cell lung cancer. Crizotinib inhibits oncogenic protein expression and impairs cellular proliferation in tumors with an overexpressed anaplastic lymphoma kinase gene. Currently used most frequently in the adult patient population, pediatric use is becoming more prominent, specifically in disease states exhibiting anaplastic lymphoma kinase-positive, metastatic disease, such as neuroblastoma. Approximately 8% of neuroblastomas have activating anaplastic lymphoma kinase-mutations, making this a promising target for a difficult-to-treat disease. Studies in the pediatric population are limited. However, targeted anaplastic lymphoma kinase-inhibitor therapies have shown improved outcomes at both one-year and two-year marks in both overall survival and progression free survival in anaplastic lymphoma kinase-positive adult patients with non-small cell lung cancer. One Children's Oncology Group phase I trial examined toxicities associated with anaplastic lymphoma kinase inhibitor therapy in pediatric patients. Results revealed varying grades in severity of neutropenia, dizziness, and liver function test elevation. In the adult population, severe toxicities reported by the manufacturer include effects on liver, cardiac and lung function. Additionally, several cases of severe, erosive, pill-esophagitis due to crizotinib therapy have been documented in the adult population. Erosive esophagitis is common in the pediatric population due to a variety of factors. Ingestion of medications or other corrosive agents accounts for approximately 3-5% (5000-10,000 cases per year) of esophagitis presentation in the pediatric population. Common causative medications include non-steroidal anti-inflammatory drugs, antibiotics such as doxycycline and tetracycline, and ferrous sulfate. Presented here is the first reported case of crizotinib-induced pill esophagitis in a pediatric patient.

Topics: Anaplastic Lymphoma Kinase; Antineoplastic Agents; Child; Crizotinib; Esophagitis; Humans; Male; Neuroblastoma; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases

Topics: Aged, 80 and over; Bedridden Persons; Crizotinib; Esophagitis; Female; Humans; Lung Neoplasms; Necrosis

Topics: Crizotinib; Esophagitis; Female; Humans; Middle Aged; Pyrazoles; Pyridines

A 44-year-old woman who was diagnosed with anaplastic lymphoma kinase-positive lung adenocarcinoma developed brain metastases, multiple spinal metastases and meningeal dissemination. Crizotinib was administered after the failure of first-line chemotherapy. Esophagitis and liver damage were induced by the twice-daily administration of crizotinib at 250 mg and 200 mg, respectively. The alternate-day administration of crizotinib (250 mg, twice daily) was able to control disease progression without any adverse effects for several months. We evaluated the relationship between the serum concentration of crizotinib and the development of esophagitis and liver damage. The alternate-day administration of crizotinib is one of the strategies for managing the severe toxicity of crizotinib.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adult; Anaplastic Lymphoma Kinase; Chemical and Drug Induced Liver Injury; Crizotinib; Drug Administration Schedule; Esophagitis; Female; Humans; Lung Neoplasms; Neoplasm Metastasis; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases; Treatment Outcome

Topics: Aged, 80 and over; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Esophagitis; Female; Humans; Lung Neoplasms; Neoplasm Staging; Prognosis; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases