The Food and Drug Administration (FDA) has approved a new indication for crizotinib (Xalkori) for the treatment of adult and pediatric patients ages one year and older who have recurrent or refractory unresectable inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors. The tumors are rare and can be benign or, less often, cancerous. These mesenchymal, soft tissue tumors most frequently affect children and adolescents. According to the National Institutes of Health's Genetic and Rare Diseases Information Center, they can occur at multiple anatomical sites-most commonly the lungs, abdomen or pelvis, and retroperitoneum. ALK-positive changes in cancer cells are related to the cell either having an altered ALK gene or making too much of the ALK protein. ALK normally helps control cell growth. ALK-positive cancer cells, however, demonstrate increased rapid growth.
Crizotinib is a kinase inhibitor that was previously approved for the treatment of
* patients with metastatic non-small cell lung cancer whose tumors are either ALK or ROS1 positive (meaning there is a mutation of the ROS1 gene), as detected by an FDA-approved test
* pediatric patients ages one year and older and young adults with relapsed or refractory systemic ALK-positive anaplastic large cell lymphoma
The safety and efficacy of crizotinib were determined in two multicenter, single-arm, open-label trials, one of which included 14 pediatric patients and the other seven adult patients who had unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumors. The major efficacy outcome was rate of objective responses, which were experienced in 12 of the 14 pediatric patients and five of the seven adult patients.
Crizotinib carries a warning that hepatotoxicity and interstitial lung disease/pneumonitis are possible. Other warnings or precautions include a risk of QT interval prolongation, bradycardia, severe visual loss, gastrointestinal toxicity (severe nausea, vomiting, diarrhea, and stomatitis) in pediatric patients with inflammatory myofibroblastic tumors, and embryo-fetal toxicity. The most common adverse effects in adult patients with inflammatory myofibroblastic tumors are vision disorders, nausea, and edema. The most common adverse effects in pediatric patients with this cancer are vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache.
Crizotinib is administered orally. Nurses should report any serious adverse effects to the FDA MedWatch reporting system at http://www.accessdata.fda.gov/scripts/medwatch/index.cfm.
For complete prescribing information for crizotinib, including actions to take regarding the dosage if adverse effects are noted, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2022/202570s033lbl.pdf.