Medical Oncology

, Volume 29, Issue 1, pp 193–198 | Cite as

Erlotinib in patients with advanced non-small-cell lung cancer: impact of dose reductions and a novel surrogate marker

  • Daniel BinderEmail author
  • Ann-Christin Buckendahl
  • Ralf-Harto Hübner
  • Peter Schlattmann
  • Bettina Temmesfeld-Wollbrück
  • Thomas Beinert
  • Norbert Suttorp
Original Paper


Erlotinib is a relatively well-tolerated treatment option for patients with advanced non-small-cell lung cancer (NSCLC). Some patients suffer from severe skin toxicity or diarrhea, making dose reductions or even treatment cessation necessary. Recent clinical trials usually defined a 100 mg daily dose as the lowest acceptable dose, whereas little is known about the efficacy with lower doses. We retrospectively reviewed the files of all patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib. We assessed demographic, disease- and treatment-related information. We tried to correlate tolerability with clinical efficacy. EGF receptor exon 18/19/21 mutations were analyzed in selected patients. Fifty-three patients with advanced non-small-cell lung cancer were treated with erlotinib. In nine patients (17%), the doses had to be reduced to 75 or 50 mg daily due to toxicity. We observed several sustained disease stabilizations in this subgroup. Patients suffering from paronychia with erlotinib had a significantly longer time to progression than did subjects without nail toxicity (P = 0.04). If patients were free from any toxicity, they were at high risk for early tumor progression (P = 0.001) and death. In patients with disease stabilization for 6 months or longer, we observed EGFR 18/19/21 wild type, exon 19 and exon 21 mutations. In conclusion, several patients required dose reductions during treatment with erlotinib. However, in tumors with sensitivity to erlotinib, even daily doses of 50–75 mg can result in sustained disease control. Paronychia represents a favorable surrogate marker for efficacy.


Lung neoplasms Drug therapy Erlotinib Dose–response relationship Drugs Drug toxicity Nail diseases 


Conflict of interest

Dr Binder received travel expenses and congress registration fees from Roche Pharma AG.


  1. 1.
    Pao W, 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. Proc Natl Acad Sci U S A. 2004;101:13306–11.PubMedCrossRefGoogle Scholar
  2. 2.
    Jackman DM, et al. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res. 2006;12:3908–14.PubMedCrossRefGoogle Scholar
  3. 3.
    Riely GJ, et al. Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res. 2006;12:839–44.PubMedCrossRefGoogle Scholar
  4. 4.
    Rosell R, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009;361:958–67.PubMedCrossRefGoogle Scholar
  5. 5.
    Cedres S, et al. Clinical surrogate markers of survival in advanced non-small cell lung cancer (NSCLC) patients treated with second-third line erlotinib. Lung Cancer. 2009;66:257–61.PubMedCrossRefGoogle Scholar
  6. 6.
    Shepherd FA, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Reck M, et al. Erlotinib in Advanced non-small cell lung cancer: efficacy and safety findings of the global phase IV Tarceva lung cancer survival treatment study. J Thorac Oncol. 2010;5:1616–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Tiseo M, et al. An expanded access program of erlotinib (Tarceva) in patients with advanced non-small cell lung cancer (NSCLC): data report from Italy. Lung Cancer. 2009;64:199–206.PubMedCrossRefGoogle Scholar
  9. 9.
    Lind JS, et al. Dramatic response to low-dose erlotinib of epidermal growth factor receptor mutation-positive recurrent non-small cell lung cancer after severe cutaneous toxicity. J Thorac Oncol. 2009;4:1585–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Yeo WL, et al. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010;5:1048–53.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Daniel Binder
    • 1
    • 5
    Email author
  • Ann-Christin Buckendahl
    • 2
  • Ralf-Harto Hübner
    • 1
  • Peter Schlattmann
    • 3
  • Bettina Temmesfeld-Wollbrück
    • 1
  • Thomas Beinert
    • 4
  • Norbert Suttorp
    • 1
  1. 1.Department of Internal Medicine/Infectious and Respiratory DiseasesCharité-Universitätsmedizin BerlinBerlinGermany
  2. 2.Department of PathologyCharité-Universitätsmedizin BerlinBerlinGermany
  3. 3.Department of Medical Statistics, Informatics and Documentation (PS)University Hospital of Friedrich-Schiller University JenaJenaGermany
  4. 4.Department of Internal Medicine/OncologyBayerwald-KlinikChamGermany
  5. 5.Medizinische Klinik m. S. Infektiologie und PneumologieCharité Universitätsmedizin BerlinBerlinGermany

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