Gefitinib response of erlotinib-refractory lung cancer involving meninges--role of EGFR mutation

Nat Clin Pract Oncol. 2006 Jan;3(1):50-7; quiz 1 p following 57. doi: 10.1038/ncponc0400.


Background: A 70-year-old Japanese-American woman who had never smoked was diagnosed with stage IV non-small-cell lung cancer with rib metastases. She had previously been well and she had no family history of malignancy. While receiving treatment with erlotinib, an epidermal growth factor receptor small-molecule inhibitor, she progressed and developed new brain metastases. She failed further chemotherapy treatments and subsequently developed extensive symptomatic leptomeningeal carcinomatosis associated with diplopia, hemiparesis, weight loss, and incontinence.

Investigations: Chest X-ray, head and chest CT scan, R2 lymph-node biopsy, histopathology, immunohistochemistry, MRI of head and spine, lumbar puncture, laser microdissection and EGFR genomic DNA sequencing of the R2 lymph node and cerebrospinal fluid tumor cells.

Diagnosis: Erlotinib-refractory stage IV lung adenocarcinoma and end-stage symptomatic leptomeningeal metastases with a novel double L858R + E884K somatic mutation of the EGFR.

Management: Carboplatin, paclitaxel and erlotinib, whole-brain radiotherapy, temozolomide with and without irinotecan, and gefitinib.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology*
  • Aged
  • Bone Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • ErbB Receptors / drug effects
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride
  • Female
  • Gefitinib
  • Humans
  • Meningeal Neoplasms / secondary*
  • Mutation
  • Quinazolines / therapeutic use*
  • Ribs / pathology*
  • Treatment Failure


  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Gefitinib