Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of gefitinib efficacy according to body surface area in patients with non-small cell lung cancer harboring an EGFR mutation

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Background

Exon 19 deletions and L858R point mutation are the most commonly encountered active epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), and they predict greater efficacy of gefitinib therapy. The objective of this study was to evaluate whether body surface area (BSA) affects the efficacy of gefitinib in patients with NSCLC harboring an active EGFR mutation.

Methods

We reviewed the medical records of consecutive patients with advanced NSCLC harboring an active EGFR mutation who received gefitinib monotherapy. The median BSA value was used as the cutoff value to evaluate the impact of BSA on the efficacy of gefitinib.

Results

The median BSA of the 103 NSCLC patients harboring an active EGFR mutation was 1.45 m2. The overall response rate, progression-free survival (PFS), and median survival time (MST) were 65.0 %, 11.3 months, and 26.2 months, respectively. There were no significant differences in clinical outcomes between the high-BSA group (BSA ≥ 1.45 m2) and low-BSA group (BSA < 1.45 m2), i.e., the response rates was 60.0 % and 69.8 %, respectively (P = 0.20), and their MST was 24.7 and 26.2 months, respectively (P = 0.78). Although BSA was predictive of PFS between high-BSA group and low-BSA group in the univariate analysis (9.0 and 12.2 months, P = 0.04), the multivariate analysis identified only performance status and smoking status as independent predictors of PFS.

Conclusions

The efficacy of gefitinib in patients with NSCLC harboring an EGFR mutation does not differ according to their BSA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E (2012) Cancer treatment and survivorship statistics, 2012. Cancer J Clin 62:220–241

    Article  Google Scholar 

  2. Mitsudomi T, Kosaka T, Endoh H, Horio Y, Hida T, Mori S (2005) Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 23:2513–2520

    Article  PubMed  CAS  Google Scholar 

  3. Yang CH, Shih JY, Chen KC, Yu CJ, Yang TY, Lin CP, Su WP, Gow CH, Hsu C, Chang GC, Yang PC (2006) Survival outcome and predictors of gefitinib antitumor activity in East Asian chemonaive patients with advanced nonsmall cell lung cancer. Cancer 107:1873–1882

    Article  PubMed  CAS  Google Scholar 

  4. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139

    Article  PubMed  CAS  Google Scholar 

  5. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  PubMed  CAS  Google Scholar 

  6. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H (2004) 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 USA 101:13306–13311

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957

    Article  PubMed  CAS  Google Scholar 

  8. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T (2010) Gefitinib or chemotherapy for non–small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388

    Article  PubMed  CAS  Google Scholar 

  9. Han JY, Park K, Kim SW, Lee DH, Kim HY, Kim HT, Ahn MJ, Yun T, Ahn JS, Suh C, Lee JS, Yoon SJ, Han JH, Lee JW, Jo SJ, Lee JS (2012) First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol 30:1122–1128

    Article  PubMed  CAS  Google Scholar 

  10. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M (2010) 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 11:121–128

    Article  PubMed  CAS  Google Scholar 

  11. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C (2011) 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 12:735–742

    Article  PubMed  CAS  Google Scholar 

  12. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A et al (2012) 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 13:239–246

    Article  PubMed  CAS  Google Scholar 

  13. Bria E, Milella M, Cuppone F, Novello S, Ceribelli A, Vaccaro V, Sperduti I, Gelibter A, Scagliotti GV, Cognetti F, Giannarelli D (2011) Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta analysis. Ann Oncol 22:2277–2285

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Petrelli F, Borgonovo K, Cabiddu M, Barni S (2012) Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non–small-cell lung cancer: a meta-analysis of 13 randomized trials. Clin Lung Cancer 13:107–114

    Article  PubMed  CAS  Google Scholar 

  15. Gao G, Ren S, Li A, Xu J, Xu Q, Su C, Guo J, Deng Q, Zhou C (2012) Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small cell lung cancer with mutated EGFR: a meta-analysis from six phase III randomized controlled trials. Int J Cancer 131:822–829

    Article  Google Scholar 

  16. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong RP, Baselga J (2003) Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol 21:2237–2246

    Article  PubMed  CAS  Google Scholar 

  17. Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC (2003) Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small lung cancer: a randomized trial. JAMA 290:2149–2158

    Article  PubMed  CAS  Google Scholar 

  18. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  PubMed  CAS  Google Scholar 

  19. Du BOIS, Du BOIS (1916) Clinical calorimetry tenth paper a formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 17:863–871

    Google Scholar 

  20. Nagai Y, Miyazawa H, Tanaka T, Udagawa K, Kato M, Fukuyama S, Yokote A, Kobayashi K, Kanazawa M, Hagiwara K (2005) 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 65:7276–7282

    Article  PubMed  CAS  Google Scholar 

  21. Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A, Okinaga S, Nagashima M, Oizumi S, Uematsu K, Nagai Y, Moriyama G, Miyazawa H, Ikebuchi K, Morita S, Kobayashi K, Hagiwara K (2010) Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 126:651–655

    Article  PubMed  CAS  Google Scholar 

  22. Ichihara E, Hotta K, Takigawa N, Kudo K, Kato Y, Honda Y, Hayakawa H, Minami D, Sato A, Tabata M, Tanimoto M, Kiura K (2013) Impact of physical size on gefitinib efficacy in patients with non-small cell lung cancer harboring EGFR mutations. Lung Cancer 81:435–439

    Article  PubMed  Google Scholar 

  23. Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, Ariyoshi Y, Fukuoka M (2006) Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 24:2549–2556

    Article  PubMed  CAS  Google Scholar 

  24. Mitsudomi T, Yatabe Y (2007) Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer. Cancer Sci 98:1817–1824

    Article  PubMed  CAS  Google Scholar 

  25. McKillop D, Hutchison M, Partridge EA, Bushby N, Cooper CM, Clarkson-Jones JA, Herron W, Swaisland HC (2004) Metabolic disposition of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in rat, dog and man. Xenobiotica 34:917–934

    Article  PubMed  CAS  Google Scholar 

  26. McKillop D, Partridge EA, Kemp JV, Spence MP, Kendrew J, Barnett S, Wood PG, Giles PB, Patterson AB, Bichat F, Guilbaud N, Stephens TC (2005) Tumor penetration of gefitinib (Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor. Mol Cancer Ther 4:641–649

    Article  PubMed  CAS  Google Scholar 

  27. Haura E, Sommers E, Becker D, McKillop D, Bepler G (2007) Pilot phase II study of preoperative gefitinib in early stage non-small cell lung cancer with assessment of intratumour gefitinib levels and tumour target modulation (abstract). J Clin Oncol 25((18 S)):7603

    Google Scholar 

  28. Pollack VA, Savage DM, Baker DA, Tsaparikos KE, Sloan DE, Moyer JD, Barbacci EG, Pustilnik LR, Smolarek TA, Davis JA, Vaidya MP, Arnold LD, Doty JL, Iwata KK, Morin MJ (1999) Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358774: dynamics of receptor inhibition in situ and antitumor effects in athymic mice. J Pharmacol Exp Ther 291:739–748

    PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara-City, Kanagawa, 252-0374, Japan

    Satoshi Igawa, Masashi Kasajima, Mikiko Ishihara, Michiko Kimura, Yasuhiro Hiyoshi, Hideyuki Niwa, Seiichiro Kusuhara, Shinya Harada, Maiko Asakuma, Sakiko Otani, Ken Katono & Noriyuki Masuda

  2. Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara-City, Kanagawa, 252-0374, Japan

    Jiichiro Sasaki

Authors
  1. Satoshi Igawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masashi Kasajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mikiko Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michiko Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuhiro Hiyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideyuki Niwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seiichiro Kusuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shinya Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maiko Asakuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sakiko Otani
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ken Katono
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jiichiro Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Noriyuki Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoshi Igawa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Igawa, S., Kasajima, M., Ishihara, M. et al. Evaluation of gefitinib efficacy according to body surface area in patients with non-small cell lung cancer harboring an EGFR mutation. Cancer Chemother Pharmacol 74, 939–946 (2014). https://doi.org/10.1007/s00280-014-2570-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-014-2570-1

Keywords

Search

Navigation