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Jeong-Seon Ryu, M.D.1, Lucia Kim, M.D.2, Chul-Hyun Kim, M.D.1, Hyun-Jung Kim, M.D.1, Jae-Hwa Cho, M.D.1
, Seung-Min Kwak, M.D.1, Hong-Lyeol Lee, M.D.1
, Seung-Min Kwak, M.D.1, Hong-Lyeol Lee, M.D.1
Abstract
Gefitinib is an oral selective inhibitor that targets the tyrosine kinase of the epidermal growth factor receptor. The prevalence of interstitial lung disease is 2% in Japan and 0.3% in the USA with a mortality rate of up to one third. We describe two non-small cell lung cancer patients who developed acute respiratory failure after gefitinib, and suggest that clinicians take extreme caution when deciding to treat patients with gefitinib.
Figures and Tables
Figure 1
Chest radiography shows newly developed pulmonary infiltrates on left lower lung field in case 1 and 2. Bilateral ground glass opacities are noted on chest CT scan of case 2.
Figure 2
It demonstrates hyaline membranes lining the alveolar wall with edema and interstitial mononuclear cell infiltrate in case 1. Fibrinoid proteinaceous exudate in the alveolar space and sometimes along the alveolar walls and intra-alveolar and interstitial infiltration of neutrophils and lymphocytes are shown in case 2.
Table 1
Summary of Death Cases from Respiratory Failure Induced by Gefitinib*
*AD=adenocarcinoma, CTx=chemotherapy, DAD=diffuse alveolar damage, IPF=idiopathic pulmonary fibrosis, L=large cell carcinoma, NE=not evaluated, PY=pack-years, RTx=radiation therapy, SQ=squamous cell carcinoma, SD=stable disease, Clinical diagnosis=diagnosis made by clinical and radiologic findings; †, response to gefitinib; ¶, Period of administration of gefitinib before the development of acute respiratory failure; ‡, post-radiation pulmonary fibrosis
References
1. Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol. 2006. 24:2549–2556.
2. Cohen MH, Williams GA, Sridhara R, Chen G, McGuinn WD Jr, Morse D, et al. United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res. 2004. 10:1212–1218.
3. Takano T, Ohe Y, Kusumoto M, Tateishi U, Yamamoto S, Nokihara H, et al. Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib. Lung Cancer. 2004. 45:93–104.
4. Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y, et al. Severe acute interstitial pneumonia and gefitinib. Lancet. 2003. 361:137–139.
5. Seto T, Seki N, Uematsu K, Tanigaki T, Shioya S, Koboyashi T, et al. Gefitinib-induced lung injury successfully treated with high-dose corticosteroids. Respirology. 2006. 11:113–116.
6. Ohyanagi F, Ando Y, Nagashima F, Narabayashi M, Sasaki Y. Acute gefitinib-induced pneumonitis. Int J Clin Oncol. 2004. 9:406–409.
7. Rabinowits G, Herchenhorn D, Rabinowits M, Weatge D, Torres W. Fatal pulmonary toxicity in a patient treated with gefitinib for non-small cell lung cancer after previous hemolytic-uremic syndrome due to gemcitabine. Anticancer Drugs. 2003. 14:665–668.
8. Ieki R, Saitoh E, Shibuya M. Acute lung injury as a possible adverse drug reaction related to gefitinib. Eur Respir J. 2003. 22:179–181.
9. Okamoto I, Fujii K, Matsumoto M, Terasaki Y, Kihara N, Kohrogi H, et al. Diffuse alveolar damage after ZD1839 therapy in a patient with non-small cell lung cancer. Lung Cancer. 2003. 40:339–342.
10. Inomata S, Takahashi H, Nagata M, Yamada G, Shiratori M, Tanaka H, et al. Acute lung injury as an adverse event of gefitinib. Anticancer Drugs. 2004. 15:461–467.
11. Nagaria NC, Cogswell J, Choe JK, Kasimis B. Side effects and good effects from new chemotherapeutic agents: case 1. Gefitinib-induced interstitial fibrosis. J Clin Oncol. 2005. 23:2423–2424.
12. Sumpter K, Harper-Wynne C, O'Brien M, Congleton J. Severe acute interstitial pneumonia and gefitinib. Lung Cancer. 2004. 43:367–368.
13. Suzuki H, Aoshiba K, Yokohori N, Nagai A. Epidermal growth factor receptor tyrosine kinase inhibition augments a murine model of pulmonary fibrosis. Cancer Res. 2003. 63:5054–5059.
14. Ishii Y, Fujimoto S, Fukuda T. Gefitinib prevents bleomycin-induced lung fibrosis in mice. Am J Respir Crit Care Med. 2006. 174:550–556.
15. Fujiwara Y, Kiura K, Toyooka S, Takigawa N, Tokumo M, Hotta K, et al. Relationship between epidermal growth factor receptor gene mutations and the severity of adverse events by gefitinib in patients with advanced non-small cell lung cancer. Lung Cancer. 2006. 52:99–103.
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