A marked response to icotinib in a patient with large cell neuroendocrine carcinoma harboring an EGFR mutation: 
A case report

Wang,Yuehong; Shen,Yi  Hong; Ma,Shanni; Zhou,Jianying

doi:10.3892/ol.2015.3405

A marked response to icotinib in a patient with large cell neuroendocrine carcinoma harboring an EGFR mutation: A case report

Authors:
- Yuehong Wang
- Yi Hong Shen
- Shanni Ma
- Jianying Zhou
View Affiliations

Affiliations: Department of Respiratory Disease, The First Affiliated Hospital of the College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: June 22, 2015 https://doi.org/10.3892/ol.2015.3405
Pages: 1575-1578

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study reports the case of an 84-year-old male with primary pulmonary large cell neuroendocrine carcinoma (LCNEC) harboring an epidermal growth factor receptor (EGFR) gene mutation that exhibited a long‑lasting response to the EGFR‑tyrosine kinase inhibitor (EGFR‑TKI) icotinib. The patient had an extensive smoking history, a poor performance status, and presented with an irregular mass in the middle lobe of the right lung on computed tomography (CT) and an enlarged left supraclavicular lymph node on physical examination. Right middle lobe bronchial brushing during fiberoptic bronchoscopy identified poorly‑differentiated cancer cells. The left supraclavicular lymph node was biopsied and a diagnosis of metastatic LCNEC was determined. Furthermore, an EGFR exon 19 deletion was identified by DNA sequencing. Following diagnosis, icotinib was administered at a dose of 125 mg three times a day. Chest CT scans were performed after 1 month of treatment, which indicated that the tumor was in partial remission. This marked response to icotinib lasted for 8 months. Thus, the present case illustrates the possibility of identifying EGFR mutations in LCNEC and indicates that EGFR‑tyrosine kinase inhibitors may be an alternative treatment strategy for patients with LCNEC harboring activating EGFR mutations.

View Figures

View References

1	Travis WD, Linnoila RI, Tsokos MG, Hitchcock CL, Cutler GB Jr, Nieman L, Chrousos G, Pass H and Doppman J: Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol. 15:529–553. 1991. View Article : Google Scholar : PubMed/NCBI
2	Rosell R1, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al: Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica: 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. 13:239–426. 2012. View Article : Google Scholar : PubMed/NCBI
3	Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361:947–957. 2009. View Article : Google Scholar : PubMed/NCBI
4	De Pas TM, Giovannini M, Manzotti M, Trifirò G, Toffalorio F, Catania C, Spaggiari L, Labianca R and Barberis M: Large-cell neuroendocrine carcinoma of the lung harboring EGFR mutation and responding to gefitinib. J Clin Oncol. 29:e819–e822. 2011. View Article : Google Scholar : PubMed/NCBI
5	Travis WD: Advances in neuroendocrine lung tumors. Ann Oncol. 21:(Sul 7). vii65–vii71. 2010. View Article : Google Scholar : PubMed/NCBI
6	Travis WD, Colby TV, Corrin B, et al: Histological Typing of Lung and Pleural Tumors. Springer-Verlag; Berlin: 1999, View Article : Google Scholar
7	Travis WD, Brambilla E, Müller-Hermelink HK, et al: Pathology and GeneticsTumours of the Lung, Pleura, Thymus and Heart. IARC Press; Lyon: 2004
8	Sun JM, Ahn MJ, Ahn JS, Um SW, Kim H, Kim HK, et al: Chemotherapy for pulmonary large cell neuroendocrine carcinoma: Similar to that for small cell lung cancer or non-small cell lung cancer? Lung Cancer. 77:365–370. 2012. View Article : Google Scholar : PubMed/NCBI
9	Takei H, Asamura H, Maeshima A, Suzuki K, Kondo H, Niki T, Yamada T, Tsuchiya R and Matsuno Y: Large cell neuroendocrine carcinoma of the lung: A clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg. 124:285–292. 2002. View Article : Google Scholar : PubMed/NCBI
10	Fournel L, Falcoz PE, Alifano M, Charpentier MC, Boudaya MS, Magdeleinat P, Damotte D and Régnard JF: Surgical management of pulmonary large cell neuroendocrine carcinomas: A 10-year experience. Eur J Cardiothorac Surg. 43:111–114. 2013. View Article : Google Scholar : PubMed/NCBI
11	Abedallaa N, Tremblay L, Baey C, Fabre D, Planchard D, Pignon JP, Guigay J, Pechoux CL, Soria JC, de Montpreville VT, et al: Effect of chemotherapy in patients with resected small-cell or large cell neuroendocrine carcinoma. J Thorac Oncol. 7:1179–1183. 2012. View Article : Google Scholar : PubMed/NCBI
12	Kozuki T, Fujimoto N, Ueoka H, Kiura K, Fujiwara K, Shiomi K, Mizobuchi K, Tabata M, Hamazaki S and Tanimoto M: Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma. J Cancer Res Clin Oncol. 131:147–151. 2005. View Article : Google Scholar : PubMed/NCBI
13	Igawa S, Watanabe R, Ito I, Murakami H, Takahashi T, Nakamura Y, Tsuya A, Kaira K, Naito T, Endo M, et al: Comparison of chemotherapy for unresectable pulmonary high-grade non-small cell neuroendocrine carcinoma and small-cell lung cancer. Lung Cancer. 68:438–445. 2010. View Article : Google Scholar : PubMed/NCBI
14	Yanagisawa S, Morikawa N, Kimura Y, Nagano Y, Murakami K and Tabata T: Large-cell neuroendocrine carcinoma with epidermal growth factor receptor mutation: Possible transformation of lung adenocarcinoma. Respirology. 17:1275–1277. 2012. View Article : Google Scholar : PubMed/NCBI
15	Popat S, Wotherspoon A, Nutting CM, Gonzalez D, Nicholson AG and O'Brien M: Transformation to ‘high grade’ neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma. Lung Cancer. 80:1–4. 2013. View Article : Google Scholar : PubMed/NCBI
16	Rossi G, Cavazza A, Marchioni A, Longo L, Migaldi M, Sartori G, Bigiani N, Schirosi L, Casali C, Morandi U, et al: Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol. 23:8774–8785. 2005. View Article : Google Scholar : PubMed/NCBI
17	Iyoda A, Travis WD, Sarkaria IS, Jiang SX, Amano H, Sato Y, Saegusa M, Rusch VW and Satoh Y: Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma. Exp Ther Med. 2:1041–1045. 2011.PubMed/NCBI