Clinical impact of continued crizotinib administration after isolated central nervous system progression in patients with lung cancer positive for ALK rearrangement

J Thorac Oncol. 2013 May;8(5):654-7. doi: 10.1097/JTO.0b013e31828c28e7.

Abstract

Introduction: Although crizotinib manifests marked antitumor activity in individuals with non-small-cell lung cancer positive for ALK abnormalities, all treated patients ultimately develop resistance to this drug. The central nervous system (CNS) is a frequent site of disease progression in such patients, with palliative radiotherapy usually being administered for the CNS metastasis. However, subsequent chemotherapy has not been optimized in these patients.

Methods: We retrospectively evaluated the continuation of crizotinib treatment after radiotherapy for isolated CNS progression in ALK-rearrangement-positive non-small-cell lung cancer patients.

Results: Among 21 ALK-rearrangement-positive patients treated with crizotinib, seven individuals resumed daily crizotinib administration after the completion of radiotherapy for isolated CNS failure. All these patients continued to receive crizotinib for at least 4 months after radiotherapy without disease progression. One patient experienced a recurrent isolated CNS failure during the second period of crizotinib administration but subsequently resumed crizotinib treatment again for at least 8.5 months after another application of radiotherapy.

Conclusions: Development of isolated CNS metastasis is emerging as a clinical concern for patients treated with crizotinib. Our data suggest that continued administration of crizotinib after radiotherapy for isolated CNS progression is a potential treatment option for such patients.

MeSH terms

  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Crizotinib
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Pyridines / therapeutic use*
  • Radiosurgery
  • Radiotherapy
  • Receptor Protein-Tyrosine Kinases / genetics
  • Retrospective Studies

Substances

  • EML4-ALK fusion protein, human
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases