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

Masayuki Takeda, Isamu Okamoto, Kazuhiko Nakagawa

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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.

Original languageEnglish
Pages (from-to)654-657
Number of pages4
JournalJournal of Thoracic Oncology
Volume8
Issue number5
DOIs
Publication statusPublished - May 1 2013

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Lung Neoplasms
Central Nervous System
Radiotherapy
Non-Small Cell Lung Carcinoma
Disease Progression
Neoplasm Metastasis
crizotinib
Drug Resistance
Therapeutics
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

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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.",
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AU - Okamoto, Isamu

AU - Nakagawa, Kazuhiko

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AB - 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.

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