Cancer Res Treat.  2016 Jan;48(1):88-97. 10.4143/crt.2014.201.

Gefitinib-Induced Interstitial Lung Disease in Korean Lung Cancer Patients

Affiliations
  • 1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. kimdw@snu.ac.kr
  • 2Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Interstitial lung disease (ILD) is a serious adverse effect of gefitinib. We examined the incidence and clinical characteristics of drug-induced ILD in Korean non-small cell lung carcinoma patients treated with gefitinib.
MATERIALS AND METHODS
A retrospective cohort study was performed in non-small cell lung cancer (NSCLC) patients who started gefitinib treatment at Seoul National University Hospital from January 2002 through December 2011. Patients who developed new abnormal radiologic findings with respiratory symptoms after gefitinib treatment were defined as having possible adverse pulmonary reactions. The patients' medical records were reviewed independently by investigators to identify the causes of pulmonary toxicities.
RESULTS
Among the 1,114 patients evaluated, 128 patients (11.5%) developed pulmonary adverse reactions after taking gefitinib. An infectious complication occurred in 98 patients (8.8%) and 15 patients (1.3%) developed ILD. Nine of the 15 patients (60.0%) with gefitinib-induced ILD experienced a fatal clinical course that met either the Common Terminology Criteria for Adverse Events grade 4 (n=3) or grade 5 (n=6). In the multivariate analysis, a lower serum albumin level (< or = 3.0 g/dL) at baseline was significantly associated with the development of gefitinib-induced ILD (odds ratio, 3.91; 95% confidence interval, 1.20 to 12.71).
CONCLUSION
The incidence of gefitinib-induced ILD in Korean NSCLC patients was similar to that reported worldwide, but lower than values reported for Japanese population. ILD was usually a life-threatening adverse effect of gefitinib, and the development of ILD was significantly associated with a lower baseline serum albumin level.

Keyword

Gefitinib; Interstitial lung diseases; Lung injury; Drug-related side effects and adverse reactions; Lung neoplasms

MeSH Terms

Asian Continental Ancestry Group
Carcinoma, Non-Small-Cell Lung
Cohort Studies
Drug-Related Side Effects and Adverse Reactions
Humans
Incidence
Lung Diseases, Interstitial*
Lung Injury
Lung Neoplasms*
Lung*
Medical Records
Multivariate Analysis
Research Personnel
Retrospective Studies
Seoul
Serum Albumin
Serum Albumin

Figure

  • Fig. 1. Outline of patient recruitment and distribution of adverse pulmonary reactions. SNUH, Seoul National University Hospital.

  • Fig. 2. Cumulative incidence of gefitinib-induced interstitial lung disease.


Reference

References

1. Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist. 2003; 8:303–6.
Article
2. 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. 2009; 361:947–57.
Article
3. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010; 362:2380–8.
Article
4. Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y, et al. Severe acute interstitial pneumonia and gefitinib. Lancet. 2003; 361:137–9.
Article
5. Min JY, Lee HY, Lim H, Ahn MJ, Park K, Chung MP, et al. Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non-small cell lung cancer: a review on current insight. Cancer Chemother Pharmacol. 2011; 68:1099–109.
Article
6. Han JY, Park K, Kim SW, Lee DH, Kim HY, Kim HT, et al. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol. 2012; 30:1122–8.
Article
7. Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, et al. Randomized Phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res. 2010; 16:1307.
Article
8. Sun JM, Lee KH, Kim SW, Lee DH, Min YJ, Yun HJ, et al. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer. 2012; 118:6234–42.
9. Kudoh S, Kato H, Nishiwaki Y, Fukuoka M, Nakata K, Ichinose Y, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med. 2008; 177:1348–57.
10. Keam B, Kim DW, Park JH, Lee JO, Kim TM, Lee SH, et al. How molecular understanding affects to prescribing patterns and clinical outcome of gefitinib in non-small cell lung cancer? 10 Year experience of single institution. Cancer Res Treat. 2013; 45:178–85.
Article
11. Vahid B, Marik PE. Pulmonary complications of novel antineoplastic agents for solid tumors. Chest. 2008; 133:528–38.
Article
12. Kang HJ, Park JS, Kim DW, Lee J, Jeong YJ, Choi SM, et al. Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients. Respir Med. 2012; 106:443–50.
Article
13. 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; 24:2549–56.
Article
14. 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.
Article
15. Hotta K, Kiura K, Tabata M, Harita S, Gemba K, Yonei T, et al. Interstitial lung disease in Japanese patients with non-small cell lung cancer receiving gefitinib: an analysis of risk factors and treatment outcomes in Okayama Lung Cancer Study Group. Cancer J. 2005; 11:417–24.
16. Nakagawa M, Nishimura T, Teramukai S, Tada H, Tanaka F, Yanagihara K, et al. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer: a retrospective analysis: JMTO LC03-02. BMC Res Notes. 2009; 2:157.
17. Hotta K, Kiura K, Takigawa N, Yoshioka H, Harita S, Kuyama S, et al. Comparison of the incidence and pattern of interstitial lung disease during erlotinib and gefitinib treatment in Japanese Patients with non-small cell lung cancer: the Okayama Lung Cancer Study Group experience. J Thorac Oncol. 2010; 5:179–84.
Article
18. Akamatsu H, Inoue A, Mitsudomi T, Kobayashi K, Nakagawa K, Mori K, et al. Interstitial lung disease associated with gefitinib in Japanese patients with EGFR-mutated non-small-cell lung cancer: combined analysis of two Phase III trials (NEJ 002 and WJTOG 3405). Jpn J Clin Oncol. 2013; 43:664–8.
Article
19. Chang SC, Chang CY, Chang SJ, Yuan MK, Lai YC, Liu YC, et al. Gefitinib-related interstitial lung disease in Taiwanese patients with non-small-cell lung cancer. Clin Lung Cancer. 2013; 14:55–61.
Article
20. 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; 63:5054–9.
21. Lateef O, Shakoor N, Balk RA. Methotrexate pulmonary toxicity. Expert Opin Drug Saf. 2005; 4:723–30.
Article
22. Li J, Brahmer J, Messersmith W, Hidalgo M, Baker SD. Binding of gefitinib, an inhibitor of epidermal growth factor receptortyrosine kinase, to plasma proteins and blood cells: in vitro and in cancer patients. Invest New Drugs. 2006; 24:291–7.
Article
23. Ter Heine R, Van den Bosch RT, Schaefer-Prokop CM, Lankheet NA, Beijnen JH, Staaks GH, et al. Fatal interstitial lung disease associated with high erlotinib and metabolite levels: a case report and a review of the literature. Lung Cancer. 2012; 75:391–7.
Article
24. Forsythe B, Faulkner K. Overview of the tolerability of gefitinib (IRESSA) monotherapy : clinical experience in non-small-cell lung cancer. Drug Saf. 2004; 27:1081–92.
25. Koo LC, Clark JA, Quesenberry CP, Higenbottam T, Nyberg F, Wolf MK, et al. National differences in reporting 'pneumonia' and 'pneumonia interstitial': an analysis of the WHO International Drug Monitoring Database on 15 drugs in nine countries for seven pulmonary conditions. Pharmacoepidemiol Drug Saf. 2005; 14:775–87.
Article
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