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      Pulsatile Erlotinib in EGFR-Positive Non-Small-Cell Lung Cancer Patients With Leptomeningeal and Brain Metastases: Review of the Literature.

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          Abstract

          Patients with epidermal growth factor receptor (EGFR)-positive (EGFR+) non-small-cell lung cancer (NSCLC) show improved response rates when treated with tyrosine kinase inhibitors (TKIs) such as erlotinib. However, standard daily dosing of erlotinib often does not reach therapeutic concentrations within the cerebrospinal fluid (CSF), resulting in progression of central nervous system (CNS) disease. Intermittent, high-dose administration of erlotinib reaches therapeutic concentrations within the CSF and is well tolerated in patients. Experience with "pulsatile" dosing, however, is limited. We review the literature on the pharmacology and clinical outcomes of pulsatile erlotinib in the treatment of EGFR+ NSCLC with brain and leptomeningeal metastases, and include available data on the use of next-generation TKIs in CNS progression. We also provide our institution's experience with patients treated with pulsatile erlotinib for CNS metastasis, and propose clinical criteria for its use. Pulsatile erlotinib is a reasonable alternative in EGFR+ patients with new or worsening CNS disease, without evidence of systemic progression, and without confirmed T790M resistance mutations within the CNS.

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          Author and article information

          Journal
          Clin Lung Cancer
          Clinical lung cancer
          Elsevier BV
          1938-0690
          1525-7304
          Jul 2017
          : 18
          : 4
          Affiliations
          [1 ] Barnes-Jewish Hospital, St Louis, MO.
          [2 ] Mallinckrodt Institute of Radiology at Washington University, St Louis, MO.
          [3 ] Division of Pharmacology, Washington University School of Medicine, St Louis, MO.
          [4 ] Division of Oncology, Washington University School of Medicine, St Louis, MO. Electronic address: mbaggstr@wustl.edu.
          Article
          S1525-7304(17)30042-6
          10.1016/j.cllc.2017.01.013
          28245967

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