Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2011

01-11-2011 | Mini Review

Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non-small cell lung cancer: a review on current insight

Authors: Ji Hye Min, Ho Yun Lee, Hoyeong Lim, Myung-Ju Ahn, Keunchil Park, Man Pyo Chung, Kyung Soo Lee

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2011

Login to get access

Abstract

Purpose

With recent advances in targeted therapy such as tyrosine kinase inhibitor (TKI) therapy for non-small cell lung cancer (NSCLC), pulmonary toxicity has emerged as a problem. The recognition of common CT findings and patterns of TKI-induced interstitial lung disease (ILD) is mandatory for achieving a timely diagnosis and for the appropriate management of this condition. Therefore, familiarity with this complicating ILD is crucial.

Methods

We reviewed all published literature in the English language regarding the ILD among NSCLC patients receiving TKIs.

Results

The previous reports focused on the incidence, mortality rate, and risk factors of TKI-induced ILDs. This review elaborates on the diverse CT findings and predominant patterns of ILDs associated with TKI therapy. Emphases will be given on the role of CT, in particular, for the diagnosis of the subacute or chronic appearance of ILDs. This review also offers information about the pathogenesis and risk factor for the development of TKI-induced ILD. Representative cases will be presented as a pictorial review.

Conclusions

It is important to recognize the various patterns of TKI-induced ILDs, which increase in incidence with the introduction of diverse types of molecularly targeted agents. Poor prognoses are expected when there is a short interval from the initiation of target therapy to the onset of ILD, acute interstitial pneumonia pattern of ILD, and preexisting pulmonary fibrosis.
Literature
1.
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(10):947–957PubMedCrossRef
2.
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388PubMedCrossRef
3.
Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y, Ebina M, Kikuchi T, Moriya T, Nukiwa T (2003) Severe acute interstitial pneumonia and gefitinib. Lancet 361(9352):137–139PubMedCrossRef
4.
Makris D, Scherpereel A, Copin M, Colin G, Brun L, Lafitte J, Marquette C (2007) Fatal interstitial lung disease associated with oral erlotinib therapy for lung cancer. BMC cancer 7(1):150PubMedCrossRef
5.
Liu V, White D, Zakowski M, Travis W, Kris M, Ginsberg M, Miller V, Azzoli C (2007) Pulmonary toxicity associated with Erlotinib*. Chest 132(3):1042–1044PubMedCrossRef
6.
Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, Ariyoshi Y, Fukuoka M (2006) Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 24(16):2549–2556PubMedCrossRef
7.
Hotta K, Kiura K, Tabata M, Harita S, Gemba K, Yonei T, Bessho A, Maeda T, Moritaka T, Shibayama T (2005) 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 11(5):417–424PubMedCrossRef
8.
Hotta K, Kiura K, Takigawa N, Yoshioka H, Harita S, Kuyama S, Yonei T, Fujiwara K, Maeda T, Aoe K, Ueoka H, Kamei H, Umemura S, Moritaka T, Segawa Y, Kawai H, Bessho A, Kato K, Tabata M, Tanimoto M (2010) 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 5(2):179–184PubMedCrossRef
9.
Takano T, Ohe Y, Kusumoto M, Tateishi U, Yamamoto S, Nokihara H, Yamamoto N, Sekine I, Kunitoh H, Tamura T (2004) 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 45(1):93–104PubMedCrossRef
10.
Seto T, Yamamoto N (2004) Interstitial lung diseases (ILD) induced by gefitinib in patients with advanced non-small cell lung cancer (NSCLC): results of a West Japan Thoracic Oncology Group (WJTOG) epidemiological survey. In: ASCO Annual Meeting Proceedings (Post-Meeting Edition), J Clin Oncol vol 22, no 14S, p 7064, July 15 2004
11.
Chou C, Ko H, Wang C, Yu C, Kuo H, Huang C (2010) Erlotinib-associated near-fatal interstitial pneumonitis in a patient with relapsed lung adenocarcinoma. Chang Gung Med J 33(1):100–105PubMed
12.
Vahid B, Esmaili A (2007) Erlotinib-associated acute pneumonitis: report of two cases. Can Respir J J Can Thorac Soc 14(3):167–170
13.
Del Castillo Y, Espinosa P, Bodi F, Alcega R, Munoz E, Rabasso C, Castander D (2010) Interstitial lung disease associated to erlotinib treatment: a case report. Cases J 3:59PubMedCrossRef
14.
Tsujino K, Kawaguchi T, Kubo A, Aono N, Nakao K, Koh Y, Tachibana K, Isa S, Takada M, Kurata T (2009) Response rate is associated with prolonged survival in patients with advanced non-small cell lung cancer treated with gefitinib or erlotinib. J Thorac Oncol 4(8):994–1001PubMedCrossRef
15.
Ratain M, Eckhardt S (2004) Phase II studies of modern drugs directed against new targets: if you are fazed, too, then resist RECIST. J Clin Oncol 22(22):4442–4445PubMedCrossRef
16.
Vahid B, Marik P (2008) Pulmonary complications of novel antineoplastic agents for solid tumors. Chest 133(2):528–538PubMedCrossRef
17.
Camus P, Kudoh S, Ebina M (2004) Interstitial lung disease associated with drug therapy. Br J Cancer 91:S18–S23PubMedCrossRef
18.
Muller N, White D, Jiang H, Gemma A (2004) Diagnosis and management of drug-associated interstitial lung disease. Br J Cancer 91:S24–S30PubMedCrossRef
19.
Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R (2003) FDA drug approval summary: Gefitinib (ZD1839)(Iressa (R)) tablets. Oncologist 8(4):303–306PubMedCrossRef
20.
Aoe K, Hiraki A, Murakami T, Maeda T, Umemori Y, Katayama H, Eda R, Takeyama H (2005) Sudden onset of interstitial lung disease induced by gefitinib in a lung cancer patient with multiple drug allergy. Anticancer Res 25(1B):415–418PubMed
21.
Endo M, Johkoh T, Kimura K, Yamamoto N (2006) Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan Thoracic Oncology Group. Lung Cancer 52(2):135–140PubMedCrossRef
22.
Um S, Lee S, Yang D, Son C, Roh M, Kim K, Lee K, Choi P (2009) Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis. Clin Respir J 3(3):181–184PubMedCrossRef
23.
Nagaria N, Cogswell J, Choe J, Kasimis B (2005) Side effects and good effects from new chemotherapeutic agents: case 1. Gefitinib-induced interstitial fibrosis. J Clin Oncol 23(10):2423–2424PubMedCrossRef
24.
Nakagawa M, Teramukai S, Tada H (2005) Hypoalbumia as a risk factor of interstitinal lung disease (ILD) during gefitinib treatment in patients with non-small cell lung cancer (NSCLC): a JMTO study. Proc ASCO 23:667s (Abstract# 7190)
25.
Cohen M, Williams G, Sridhara R, Chen G, McGuinn W, Morse D, Abraham S, Rahman A, Liang C, Lostritto R (2004) United States food and drug administration drug approval summary. Clin Cancer Res 10(4):1212–1218PubMedCrossRef
26.
Cohen M, Johnson J, Chen Y, Sridhara R, Pazdur R (2005) (Tarceva (R)) tablets. Oncologist 10(7):461–466PubMedCrossRef
27.
Herbst R, Prager D, Hermann R, Fehrenbacher L, Johnson B, Sandler A, Kris M, Tran H, Klein P, Li X (2005) TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 23(25):5892–5899PubMedCrossRef
28.
Gemma A (2009) Drug-induced interstitial lung diseases associated with molecular-targeted anticancer agents. J Nippon Med School 76(1):4–8CrossRef
29.
Dempke WC, Suto T, Reck M (2010) Targeted therapies for non-small cell lung cancer. Lung Cancer 67(3):257–274PubMedCrossRef
30.
Wheatley-Price P, Shepherd F (2008) Targeting angiogenesis in the treatment of lung cancer. J Thorac Oncol 3(10):1173–1184PubMedCrossRef
31.
Ide S, Soda H, Hakariya T, Takemoto S, Ishimoto H, Tomari S, Sawai T, Nagashima S, Furukawa M, Nakamura Y (2010) Interstitial pneumonia probably associated with sorafenib treatment: an alert of an adverse event. Lung Cancer 67(2):248–250PubMedCrossRef
32.
Keogh BA, Crystal RG (1982) Alveolitis: the key to the interstitial lung disorders. Thorax 37(1):1–10PubMedCrossRef
33.
Selman M, King TE, Pardo A (2001) Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 134(2):136–151PubMed
34.
Suzuki H, Aoshiba K, Yokohori N, Nagai A (2003) Epidermal growth factor receptor tyrosine kinase inhibition augments a murine model of pulmonary fibrosis. Cancer Res 63(16):5054–5059PubMed
35.
Higenbottam T, Kuwano K, Nemery B, Fujita Y (2004) Understanding the mechanisms of drug-associated interstitial lung disease. Br J Cancer 91:S31–S37PubMedCrossRef
36.
Kuwano K, Hagimoto N, Maeyama T, Fujita M, Yoshimi M, Inoshima I, Nakashima N, Hamada N, Watanabe K, Hara N (2002) Mitochondria-mediated apoptosis of lung epithelial cells in idiopathic interstitial pneumonias. Lab Invest 82(12):1695–1706PubMed
37.
Aida S, Tamai S, Sekiguchi S, Shimizu N (1994) Distribution of epidermal growth factor and epidermal growth factor receptor in human lung: immunohistochemical and immunoelectron-microscopic studies. Respiration 61(3):161–166PubMedCrossRef
38.
Ryu J (2010) Chemotherapy-induced pulmonary toxicity in lung cancer patients. J Thorac Oncol 5(9):1313–1314PubMedCrossRef
39.
Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC (2000) Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics 20(5):1245–1259PubMed
40.
Tagliabue M, Casella T, Zincone G, Fumagalli R, Salvini E (1994) CT and chest radiography in the evaluation of adult respiratory distress syndrome. Acta Radiol 35(3):230–234PubMed
41.
Hansell D, Bankier A, MacMahon H, McLoud T, Muller N, Remy J (2008) Fleischner society: glossary of terms for thoracic imaging1. Radiology 246(3):697–722PubMedCrossRef
42.
Lynch D, Travis W, Muller N, Galvin J, Hansell D, Grenier P, King T Jr (2005) Idiopathic interstitial pneumonias: CT features1. Radiology 236(1):10–21PubMedCrossRef
43.
Ryu J, Myers J, Swensen S (2003) Bronchiolar disorders. Am J Respir Crit Care Med 168(11):1277–1292PubMedCrossRef
44.
Visscher DW, Myers JL (2006) Bronchiolitis: the pathologist’s perspective. Proc Am Thorac Soc 3(1):41–47PubMedCrossRef
45.
Dodd J, Lee K, Johkoh T, Muller N (2006) Drug-associated organizing pneumonia: high-resolution CT findings in 9 patients. J Thorac Imaging 21(1):22–26PubMedCrossRef
46.
Isabela C, Silva S, Muller N (2006) Drug-induced lung diseases: most common reaction patterns and corresponding high-resolution CT manifestations. Semin Ultrasound CT MR 27(2):111–116CrossRef
47.
Katzenstein A, Myers J (1998) Idiopathic pulmonary fibrosis. Clinical relevance of pathologic classification. Am J Respir Crit Care Med 157(4):1301–1315PubMed
48.
Muller N, Fraser R, Lee K, Johkoh T (2003) Diseases of the lung: radiologic and pathologic correlations. Lippincott Williams & Wilkins, Philadelphia
49.
Yoh K, Kenmotsu H, Yamaguchi Y, Kubota K, Ohmatsu H, Goto K, Niho S, Ohe Y, Saijo N, Nishiwaki Y (2010) Severe interstitial lung disease associated with amrubicin treatment. J Thorac Oncol 5(9):1435–1438PubMedCrossRef
50.
Yoneda KY, Shelton DK, Beckett LA, Gandara DR (2007) Independent review of interstitial lung disease associated with death in TRIBUTE (paclitaxel and carboplatin with or without concurrent erlotinib) in advanced non-small cell lung cancer. J Thorac Oncol 2(6):537–543PubMedCrossRef
51.
Park S, Kim A, Park J, Shin C, Nam H, Kim L, Cho J, Ryu J, Kwak S (2009) Recurrent erlotinib-induced interstitial lung disease on non-small cell lung cancer. Tuberc Respir Dis 67(5):445–448CrossRef
Metadata
Title
Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non-small cell lung cancer: a review on current insight
Authors
Ji Hye Min
Ho Yun Lee
Hoyeong Lim
Myung-Ju Ahn
Keunchil Park
Man Pyo Chung
Kyung Soo Lee
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-011-1737-2

Other articles of this Issue 5/2011

Cancer Chemotherapy and Pharmacology 5/2011 Go to the issue

Original Article

Role of 12-lipoxygenase in regulation of ovarian cancer cell proliferation and survival

Original Article

Single nucleotide polymorphisms of CYP19A1 predict clinical outcomes and adverse events associated with letrozole in patients with metastatic breast cancer

Original Article

Thiopurine methyltransferase polymorphisms and mercaptopurine tolerance in Turkish children with acute lymphoblastic leukemia

Original Article

Efficacy and pharmacokinetic/pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer

Original Article

Furanodienone induces cell cycle arrest and apoptosis by suppressing EGFR/HER2 signaling in HER2-overexpressing human breast cancer cells

Original Article

Phase I trial of metronomic oral vinorelbine in patients with advanced cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits