Medical Oncology

, 30:349 | Cite as

Comparison of adverse events and efficacy between gefitinib and erlotinib in patients with non-small-cell lung cancer: a retrospective analysis

  • Tsukasa Yoshida
  • Kazuhiko Yamada
  • Koichi Azuma
  • Akihiko Kawahara
  • Hideyuki Abe
  • Satoshi Hattori
  • Fumie Yamashita
  • Yoshiaki Zaizen
  • Masayoshi Kage
  • Tomoaki Hoshino
Original Paper

Abstract

Previous studies have demonstrated that both gefitinib and erlotinib are markedly effective for the treatment of non-small-cell lung cancer (NSCLC) with somatic activating mutations of the epidermal growth factor receptor gene (EGFR-mt). These agents are considered to act on EGFR through the same mechanism. However, the efficacy of these agents against EGFR wild-type (-wt) NSCLC remains unclear, and the frequency of adverse events (AEs) appears to differ between them at each approved dose. Here, we conducted a retrospective analysis of AEs and drug efficacy in patients with NSCLC whose EGFR mutation status had been confirmed and who all received 250 mg gefitinib or 150 mg erlotinib once daily. The erlotinib group (n = 35) had more AEs, including rash, fatigue, stomatitis, anorexia and constipation. On the other hand, liver dysfunction and nail change were more frequent in the gefitinib group (n = 107). AEs of ≥grade 2, including rash, fatigue and nausea, were more frequent in the erlotinib group. The erlotinib group also showed more of a tendency to require dose reduction due to AEs. With regard to treatment efficacy for patients with EGFR-wt, there was no significant difference in progression-free survival between the two drug groups. However, this study has several limitations as of the nature of retrospective design; our data suggest that gefitinib and erlotinib might have almost equal efficacy for patients with EGFR-wt NSCLC, as is the case for patients with EGFR-mt tumors, although erlotinib appears to have higher toxicity than gefitinib at each approved dose.

Keywords

Gefitinib Erlotinib Adverse event Efficacy Comparison 

References

  1. 1.
    Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.PubMedCrossRefGoogle Scholar
  2. 2.
    Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.PubMedCrossRefGoogle Scholar
  3. 3.
    Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12:735–42.PubMedCrossRefGoogle Scholar
  6. 6.
    Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–46.PubMedCrossRefGoogle Scholar
  7. 7.
    Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.PubMedCrossRefGoogle Scholar
  8. 8.
    Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005;366:1527–37.PubMedCrossRefGoogle Scholar
  10. 10.
    Nagai Y, Miyazawa H, Huqun, et al. Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp. Cancer Res. 2005;65:7276–82.Google Scholar
  11. 11.
    Kosaka T, Yatabe Y, Endoh H, et al. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004;64:8919–23.PubMedCrossRefGoogle Scholar
  12. 12.
    Li J, Karlsson MO, Brahmer J, et al. CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst. 2006;98:1714–23.PubMedCrossRefGoogle Scholar
  13. 13.
    Tan AR, Yang X, Hewitt SM, et al. Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. J Clin Oncol. 2004;22:3080–90.PubMedCrossRefGoogle Scholar
  14. 14.
    Yeo WL, Riely GJ, Yeap BY, 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
  15. 15.
    Lind JS, Postmus PE, Heideman DA, 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
  16. 16.
    Takeda M, Okamoto I, Fukuoka M, et al. Successful treatment with erlotinib after gefitinib-related severe hepatotoxicity. J Clin Oncol. 2010;28:e273–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Kijima T, Shimizu T, Nonen S, et al. Safe and successful treatment with erlotinib after gefitinib-induced hepatotoxicity: difference in metabolism as a possible mechanism. J Clin Oncol. 2011;29:e588–90.PubMedCrossRefGoogle Scholar
  18. 18.

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Tsukasa Yoshida
    • 1
  • Kazuhiko Yamada
    • 1
  • Koichi Azuma
    • 1
  • Akihiko Kawahara
    • 2
  • Hideyuki Abe
    • 2
  • Satoshi Hattori
    • 3
  • Fumie Yamashita
    • 1
  • Yoshiaki Zaizen
    • 1
  • Masayoshi Kage
    • 2
  • Tomoaki Hoshino
    • 1
  1. 1.Division of Respirology, Neurology, and Rheumatology, Department of Internal MedicineKurume University School of MedicineKurume City, FukuokaJapan
  2. 2.Department of Diagnostic PathologyKurume University HospitalFukuokaJapan
  3. 3.Biostatistics CenterKurume UniversityFukuokaJapan

Personalised recommendations