Lubcke Nicole, Van Camp Kevin
1 University of Wisconsin Hospitals and Clinics, American Family Children's Hospital, Madison, WI, USA.
2 School of Pharmacy, University of Wisconsin, Madison, WI, USA.
J Oncol Pharm Pract. 2019 Apr;25(3):724-726. doi: 10.1177/1078155217752537. Epub 2018 Jan 22.
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.
克唑替尼是一种口服酪氨酸激酶抑制剂，于2011年获美国食品药品监督管理局（FDA）批准，用于治疗间变性淋巴瘤激酶（ALK）阳性的转移性非小细胞肺癌。克唑替尼可抑制致癌蛋白表达，并抑制ALK基因过表达肿瘤中的细胞增殖。目前该药在成年患者群体中使用最为频繁，在儿科中的应用也日益突出，特别是在表现为ALK阳性转移性疾病的病症中，如神经母细胞瘤。约8%的神经母细胞瘤存在ALK激活突变，这使其成为这种难治性疾病的一个有前景的靶点。针对儿科人群的研究有限。然而，在ALK阳性的成年非小细胞肺癌患者中，靶向ALK抑制剂疗法在1年和2年的总生存期及无进展生存期方面均显示出更好的疗效。儿童肿瘤学组的一项I期试验研究了儿科患者中ALK抑制剂治疗相关的毒性。结果显示中性粒细胞减少、头晕和肝功能检查升高的严重程度各不相同。在成年人群中，制造商报告的严重毒性包括对肝脏、心脏和肺功能的影响。此外，在成年人群中已有多例因克唑替尼治疗导致严重糜烂性药源性食管炎的记录。由于多种因素，糜烂性食管炎在儿科人群中很常见。药物或其他腐蚀性物质的摄入约占儿科人群食管炎病例的3%-5%（每年5000-10000例）。常见的致病药物包括非甾体抗炎药、强力霉素和四环素等抗生素以及硫酸亚铁。本文报告了首例儿科患者因克唑替尼导致药源性食管炎的病例。
