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

Abstract

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.

• Authors: S Wang, J Chen, Z Xie, L Xia, W Luo, J Li, Q Li, Z Yang
• Journal: Journal of clinical pharmacy and therapeutics (J Clin Pharm Ther) Vol. 42 Issue 5 Pg. 627-630 (Oct 2017) ISSN: 1365-2710 [Electronic] England
• PMID: 28667686 (Publication Type: Case Reports)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyrazoles
• Pyridines
• Crizotinib
• ALK protein, human
• Anaplastic Lymphoma Kinase
• Receptor Protein-Tyrosine Kinases

Topics

• Adult
• Anaplastic Lymphoma Kinase
• Antineoplastic Agents (administration & dosage, pharmacology)
• Brain Neoplasms (drug therapy, secondary)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Crizotinib
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Prognosis
• Protein Kinase Inhibitors (administration & dosage, pharmacology)
• Pyrazoles (administration & dosage, pharmacology)
• Pyridines (administration & dosage, pharmacology)
• Receptor Protein-Tyrosine Kinases (antagonists & inhibitors)
• Treatment Outcome