Clinical Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics
4 years ago

Pulsatile crizotinib treatment for brain metastasis in a patient with non-small-cell lung cancer

Pulsatile crizotinib treatment for brain metastasis in a patient with non-small-cell lung cancer
J. Li, Z. Xie, J. Chen, Z. Yang, S. Wang, Q. Li, W. Luo, L. Xia
What is known and objective Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib. Patients with this cancer variant have a dismal prognosis and limited treatment options when it has progressed to intracranial metastasis because of inadequate drug penetration into the central nervous system (CNS). Factors associated with response to TKI therapy have been reported to include pharmacokinetic and biodynamic resistance phenomena. Case description In our NSCLC patient with multiple intracranial metastases, we administered high-dose pulsatile crizotinib therapy (1000 mg/d) on a one-day-on/one-day-off basis. A significant central nervous system (CNS) response was achieved, and time to neurological progression was prolonged to 6 months. What is new and conclusion High-dose pulsatile therapy may be an effective dosing strategy for crizotinib in NSCLC showing progression to metastasis in the brain. In an NSCLC patient with multiple intracranial metastases, we administered high-dose pulsatile crizotinib therapy (1000 mg/day) on a one-day-on/one-day-off basis. A significant central nervous system (CNS) response was achieved and time to neurological progression was prolonged to 6 months.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jcpt.12550

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