Gefitinib is a medication that was originally developed as an epidermal growth factor receptor (EGFR) blocker. It has been used to treat non-small cell lung cancer with varying success. We describe a patient who presented with Pancoasts syndrome and after being deemed surgically unresectable had limited success with chemotherapy and radiation but had an excellent response to the medication Gefitinib. The patient was disease free for several years and after 11 years of follow up with CT scans, a PET CT showed an isolated area of FDG avidity which on biopsy was small cell carcinoma of the lung. The patient had been maintained continually on Iressa for 11 years. Gefitinib treatment and continuing EGFR blockade invariably result in resistance to the medication and ultimate relapse. However in the present case, presumed sensitivity of the original tumor was noted for a prolonged time period, with development of either a new, small cell lung cancer, or histologic transformation. Similar cases have described this phenomenon of epithelial cancers treated with tyrosine kinase inhibitor blockade and development of small cell lung cancer however our case is unusual in that this transformation is observed over an eleven year time horizon.
Conflict(s) of Interest
References with DOI
1. American Cancer Society Cancer facts and Figures. American Cancer Society, Atlanta, GA USA 2012.
2. Hirsch FR, Varella-Garcia M, Bunn PA, Di maria MV, Veve R, Bremmes RM et al. Epidermal growth factor receptor in non small cell lung cancer. N Engl J Med. 2002;346:92-98.
3. Paez JG, Janne PA, Lee JC, Tracy S Greulich H, Gabriel S et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497-1500. https://doi.org/10.1126/science.1099314
4. Engelman JA, Janne PA. Mechanisms of acquired resistence to epidermal growth factor receptor tyrosine kinase inhibitors in non small cell lung cancer. Clin Cancer Res. 2008;14:2895-2899. https://doi.org/10.1158/1078-0432.ccr-07-2248
5. Fukuoka M et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011Jul 20;29(21):2866- 74. https://doi.org/10.1200/jco.2010.33.4235
6. Douillard JY et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110:55-62. https://doi.org/10.1038/bjc.2013.721
7. Jiang S, Zhao J, Wang M et al. Small-cell lung cancer transformation in patients with pulmonary adenocarcinoma: a case report and review of literature. Medicine. 2016;95(6):e2752. https://doi.org/10.1097/md.0000000000002752
8. Sequist LV, Waltman BA, Santagata DD et al. Genotypic and histologic evolution of lung cancers acquiring resistance to EGFR inhibitors. Science Translational Medicine. 2011;3(75):75ra26. https://doi.org/10.1126/scitranslmed.3002003
9. Ware KE, Marshall ME, Heasley LR et al. Rapidly acquired resistence to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression. B PLoS One. 2010;5(11)e14117. https://doi.org/10.1371/journal.pone.0014117
Cooper, Mark H.
"Favorable Response of Advanced Superior Sulcus Non-Small Cell Lung Carcinoma to Gefitinib for 11 years complicated by Interval Development of Small Cell Carcinoma of the Lung.,"
Marshall Journal of Medicine:
1, Article 8.
Available at: http://mds.marshall.edu/mjm/vol4/iss1/8