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01-10-2015 | Original Article

First-line gefitinib treatment in elderly patients (aged ≥75 years) with non-small cell lung cancer harboring EGFR mutations

Authors: Tomohito Kuwako, Hisao Imai, Tomomi Masuda, Yosuke Miura, Kaori Seki, Reiko Yoshino, Kyoichi Kaira, Mitsuyoshi Utsugi, Kimihiro Shimizu, Noriaki Sunaga, Yoshio Tomizawa, Shinichi Ishihara, Takao Ishizuka, Akira Mogi, Takeshi Hisada, Koichi Minato, Atsushi Takise, Ryusei Saito, Masanobu Yamada

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015

Abstract

Purpose

The efficacy of gefitinib [an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor] in elderly patients with non-small cell lung cancer (NSCLC) and EGFR mutation has not been elucidated. Therefore, the objective of this study was to investigate the efficacy and feasibility of gefitinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations.

Methods

We retrospectively evaluated the clinical effects of gefitinib as a first-line treatment for elderly (≥75 years) NSCLC patients with EGFR mutations (exon 19 deletion or exon 21 L858R mutation). All patients were initially treated with gefitinib (250 mg/day) at seven institutions.

Results

Between January 2006 and December 2012, 62 patients (17 men, 45 women) with a median age of 80 years (range, 75–89 years) were included in our analysis. The overall response and disease control rates were 61.2 and 83.8 %, respectively, and the median progression-free survival and overall survival were 13.2 and 19.0 months, respectively. Common adverse events included rash, diarrhea, and liver dysfunction. Major grade 3 or 4 toxicities included skin rash (3.2 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (21.0 %). Gefitinib treatment was discontinued owing to adverse events of liver dysfunction in 3 patients, drug-induced pneumonitis in 2, and diarrhea in 1.

Conclusion

First-line gefitinib could be a preferable standard treatment in elderly patients with advanced NSCLC harboring sensitive EGFR mutations.

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. CA Cancer J Clin 62:220–241. doi:10.3322/caac.21149 CrossRefPubMed

Davidoff AJ, Tang M, Seal B, Edelman MJ (2010) Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 28:2191–2197. doi:10.1200/JCO.2009.25.4052 CrossRefPubMed

Owonikoko TK, Ragin CC, Belani CP, Oton AB, Gooding WE, Taioli E, Ramalingam SS (2007) Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol 25:5570–5577CrossRefPubMed

Gridelli C, Shepherd FA (2005) Chemotherapy for elderly patients with non-small cell lung cancer: a review of the evidence. Chest 128:947–957CrossRefPubMed

Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E, ESMO Guidelines Working Group (2012) Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii56–vii64CrossRefPubMed

Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, Olak J, Stover D, Strawn JR, Turrisi AT, Somerfield MR, American Society of Clinical Oncology (2004) American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 22:330–353CrossRefPubMed

Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M (2006) Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol 24:3657–3663CrossRefPubMed

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. doi:10.1056/NEJMoa0810699 CrossRefPubMed

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. doi:10.1016/S1470-2045(09)70364-X CrossRefPubMed

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, West Japan Oncology Group (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. doi:10.1016/S1470-2045(09)70364-X CrossRefPubMed

11.

Inoue A, Kobayashi K, Usui K, Maemondo M, Okinaga S, Mikami I, Ando M, Yamazaki K, Saijo Y, Gemma A, Miyazawa H, Tanaka T, Ikebuchi K, Nukiwa T, Morita S, Hagiwara K, North East Japan Gefitinib Study Group (2009) First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol 27:1394–1400CrossRefPubMed

12.

Morita S, Okamoto I, Kobayashi K, Yamazaki K, Asahina H, Inoue A, Hagiwara K, Sunaga N, Yanagitani N, Hida T, Yoshida K, Hirashima T, Yasumoto K, Sugio K, Mitsudomi T, Fukuoka M, Nukiwa T (2009) Combined survival analysis of prospective clinical trials of gefitinib for non-small cell lung cancer with EGFR mutations. Clin Cancer Res 15:4493–4498. doi:10.1158/1078-0432.CCR-09-0391 CrossRefPubMed

13.

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. doi:10.1200/JCO.2011.36.8456 CrossRefPubMed

14.

Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T, North-East Japan Study Group (2013) Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naive non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol 24:54–59. doi:10.1093/annonc/mds214 CrossRefPubMed

15.

Ebi N, Semba H, Tokunaga SJ, Takayama K, Wataya H, Kuraki T, Yamamoto H, Akamine SJ, Okamoto I, Nakanishi Y, Lung Oncology Group in Kyushu, Japan (2008) A phase II trial of gefitinib monotherapy in chemotherapy-naive patients of 75 years or older with advanced non-small cell lung cancer. J Thorac Oncol 3:1166–1171. doi:10.1097/JTO.0b013e318186a88d CrossRefPubMed

16.

Asami K, Koizumi T, Hirai K, Ameshima S, Tsukadaira A, Morozumi N, Morikawa A, Atagi S, Kawahara M (2011) Gefitinib as first-line treatment in elderly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung Cancer Research Group study. Clin Lung Cancer 12:387–392. doi:10.1016/j.cllc.2011.02.004 CrossRefPubMed

17.

Maemondo M, Minegishi Y, Inoue A, Kobayashi K, Harada M, Okinaga S, Morikawa N, Oizumi S, Tanaka T, Isobe H, Kudoh S, Hagiwara K, Nukiwa T, Gemma A (2012) First-line gefitinib in patients aged 75 or older with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations: NEJ 003 study. J Thorac Oncol 7:1417–1422CrossRefPubMed

18.

Fujita S, Katakami N, Masago K, Yoshioka H, Tomii K, Kaneda T, Hirabayashi M, Kunimasa K, Morizane T, Mio T (2012) Customized chemotherapy based on epidermal growth factor receptor mutation status for elderly patients with advanced non-small-cell lung cancer: a phase II trial. BMC Cancer 12:185. doi:10.1186/1471-2407-12-185 PubMedCentralCrossRefPubMed

19.

Takahashi K, Saito H, Hasegawa Y, Ando M, Yamamoto M, Kojima E, Sugino Y, Kimura T, Nomura F, Ogasawara T, Shindoh J, Yoshida N, Suzuki R (2014) First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901. Cancer Chemother Pharmacol 74:721–727. doi:10.1007/s00280-014-2548-z CrossRefPubMed

20.

Uruga H, Kishi K, Fujii T, Beika Y, Enomoto T, Takaya H, Miyamoto A, Morokawa N, Kurosaki A, Yoshimura K (2010) Efficacy of gefitinib for elderly patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor gene mutations: a retrospective analysis. Intern Med 49:103–107CrossRefPubMed

21.

Tateishi K, Ichiyama T, Hirai K, Agatsuma T, Koyama S, Hachiya T, Morozumi N, Shiina T, Koizumi T (2013) Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group study. Med Oncol 30:450. doi:10.1007/s12032-012-0450-2 CrossRefPubMed

22.

Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, Postmus PE, Rusch V, Sobin L, International Association for the Study of Lung Cancer International Staging Committee; Participating Institutions (2007) The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2:706–714CrossRefPubMed

23.

Nagai Y, Miyazawa H, Huqun 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 65:7276–7282CrossRefPubMed

24.

Yatabe Y, Hida T, Horio Y, Kosaka T, Takahashi T, Mitsudomi T (2006) A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer. J Mol Diagn 8:335–341PubMedCentralCrossRefPubMed

25.

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. doi:10.1016/j.ejca.2008.10.026 CrossRefPubMed

26.

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 98:1817–1824CrossRefPubMed

Title: First-line gefitinib treatment in elderly patients (aged ≥75 years) with non-small cell lung cancer harboring EGFR mutations
Authors: Tomohito Kuwako
Hisao Imai
Tomomi Masuda
Yosuke Miura
Kaori Seki
Reiko Yoshino
Kyoichi Kaira
Mitsuyoshi Utsugi
Kimihiro Shimizu
Noriaki Sunaga
Yoshio Tomizawa
Shinichi Ishihara
Takao Ishizuka
Akira Mogi
Takeshi Hisada
Koichi Minato
Atsushi Takise
Ryusei Saito
Masanobu Yamada
Publication date: 01-10-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2841-5

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