CSF Concentration of the Anaplastic Lymphoma Kinase Inhibitor Crizotinib

We describe the case of a 29-year-old white man with a neversmoking history and EML4-ALK-E20A20 stage IV non-small-cell lung cancer (NSCLC) whose disease had progressed after first-line cisplatin plus pemetrexed and second-line erlotinib. He started crizotinib at 200 mg twice daily and attained significant symptomatic improvement and minor tumor regression of his intrathoracic disease best classified as stable disease. 1 Before start of therapy, brain imaging studies showed no abnormalities. His systemic disease retained radiographic control with crizotinib when he presented with new-onset headaches 7.5 months into his treatment course. Magnetic resonance imaging of the brain disclosed small enhancing masses throughout the supratentorial and infratentorial brain, as well as the leptomeninges. The sagittal view of the T1-weighted sequence shows these masses, with black arrows highlighting some of the lesions (Fig 1). CSF cytology was positive for malignant cells. The patient received 30 Gy of whole-brain radiotherapy. Crizotinib was restarted at 250 mg twice daily during month 8 after the initiation of drug. Two weeks later, CSF and plasma were sampled 5 hours after a dose of crizotinib 250 mg. Concentrations of crizotinib were measured using a validated high-D I A G N O S I S I N O N C O L O G