A phase I/II study of weekly high‐dose erlotinib in previously treated patients with nonsmall cell lung cancer

Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high‐dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC).

[1]  M. Ebina,et al.  Severe acute interstitial pneumonia and gefitinib , 2003, The Lancet.

[2]  M. Sliwkowski,et al.  Preclinical studies with Erlotinib (Tarceva). , 2003, Seminars in oncology.

[3]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[4]  R. Wilson,et al.  EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Elisa Rossi,et al.  Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  M. Kris,et al.  Phase I/II trial of gefitinib and RAD001 (everolimus) in patients (pts) with advanced non-small cell lung cancer (NSCLC) , 2005 .

[7]  David Cella,et al.  Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. , 2003, JAMA.

[8]  William Pao,et al.  Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  C. Mountain,et al.  Revisions in the International System for Staging Lung Cancer. , 1997, Chest.

[10]  R. Pazdur,et al.  FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. , 2003, The oncologist.

[11]  T. Shibata,et al.  Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  G. Mills,et al.  Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors , 2003, Oncogene.

[13]  G. Giovino.  Epidemiology of tobacco use in the United States , 2002, Oncogene.

[14]  E K Rowinsky,et al.  Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  M. Kris,et al.  Cigarette smoking history predicts sensitivity to erlotinib: Results of a phase II trial in patients with bronchioloalveolar carcinoma (BAC). , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  J. Rigas,et al.  Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Elisa Rossi,et al.  Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. , 2005, Journal of the National Cancer Institute.

[18]  J. Baselga,et al.  Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. , 2001, Cancer research.

[19]  M. Kris,et al.  Practical management of patients with non-small-cell lung cancer treated with gefitinib. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  Q. She,et al.  Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[21]  G. Giaccone,et al.  Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  William Pao,et al.  Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  J. Baselga,et al.  Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[25]  M. Christian,et al.  [New guidelines to evaluate the response to treatment in solid tumors]. , 2000, Bulletin du cancer.

[26]  Renato Martins,et al.  Erlotinib in previously treated non-small-cell lung cancer. , 2005, The New England journal of medicine.

[27]  J. Minna,et al.  Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. , 2006, Journal of the National Cancer Institute.

[28]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[29]  Y. Yatabe,et al.  Epidermal growth factor receptor mutations in lung cancers , 2007, Pathology international.

[30]  Lesley Seymour,et al.  Erlotinib in lung cancer - molecular and clinical predictors of outcome. , 2005, The New England journal of medicine.

[31]  M Van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. , 2000, Journal of the National Cancer Institute.

[32]  M. Hidalgo,et al.  Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.