Drug Safety

, Volume 28, Issue 2, pp 103–113 | Cite as

Interstitial Lung Disease in Lung Cancer

Separating Disease Progression from Treatment Effects
  • Sarah Danson
  • Fiona Blackhall
  • Paul Hulse
  • Malcolm Ranson
Leading Article

Abstract

Lung cancer often develops in individuals with pre-existing pulmonary and cardiac pathology. Many of these individuals with pre-existing pathology are also at risk of occupational lung disease. New and worsening symptoms can be secondary to pre-existing pathology, progressive cancer or treatment. Pulmonary toxicity, including interstitial lung disease, following radiotherapy and conventional cytotoxic chemotherapy (e.g. cyclophosphamide, bleomycin), has been recognised for many years. Pulmonary toxicity also occurs with the newer classes of cytotoxic agents, including the deoxycytidine analogue gemcitabine. A small percentage (0.88%) of patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib have developed interstitial lung disease. This complication has been reported at a higher frequency in Japanese patients than in US patients (1.9% vs 0.34%, respectively) and in those with pre-existing pulmonary fibrosis. This review discusses the difficulties in both recognition and treatment of gefitinib-associated interstitial lung disease. Symptoms are vague, such as dyspnoea, cough and fever and can be difficult to differentiate from progressive disease, co-existing morbidity and new pulmonary pathology. Diagnosis is, therefore, by rigorous investigation to exclude all other differential diagnoses. Treatment, at present, is supportive and includes discontinuation of gefitinib, oxygen supplementation, high-dose corticosteroids and antibacterials.

References

  1. 1.
    Comis RL. A brief history of the research and treatment of lung cancer from 1970 to 2003. Int J Clin Oncol 2003; 8 (4): 230–3CrossRefGoogle Scholar
  2. 2.
    Schwarz MI, King Jr TE. Interstitial lung disease. Hamilton (ON): BC Decker, 1998Google Scholar
  3. 3.
    Abid SH, Malhotra V, Perry MC. Radiation-induced and chemotherapy-induced pulmonary injury. Curr Opin Oncol 2001; 13: 242–8PubMedCrossRefGoogle Scholar
  4. 4.
    Rossi SE, Erasmus JJ, McAdams HP, et al. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics 2000; 20: 1245–59PubMedGoogle Scholar
  5. 5.
    Okamoto I, Fujii K, Matsumoto M, et al. Diffuse alveolar damage after ZD1839 therapy in a patient with non-small cell lung cancer. Lung Cancer 2003; 40: 339–42PubMedCrossRefGoogle Scholar
  6. 6.
    Inoue A, Saijo Y, Maemondo M, et al. Severe acute interstitial pneumonia and gefitinib. Lancet 2003; 361: 137–9PubMedCrossRefGoogle Scholar
  7. 7.
    Kinoshita A, Fukuda M, Nagashima S, et al. Pulmonary damage during gefitinib monotherapy in patients with non-small cell lung cancer [abstract]. Proc Am Soc Clin Oncol 2003; 22: 698Google Scholar
  8. 8.
    Sethi JM, Rochester CL. Smoking and chronic obstructive pulmonary disease. Clin Chest Med 2000; 21(1): 67–86PubMedCrossRefGoogle Scholar
  9. 9.
    Critchley JA, Capewell S. Mortality risk associated with smoking cessation in patients with coronary heart disease: a systematic review. JAMA 2003; 290(1): 86–97PubMedCrossRefGoogle Scholar
  10. 10.
    Ryu JH, Colby TV, Hartman TE, et al. Smoking-related interstitial lung disease: a concise review. Eur Respir J 2001; 17(1): 122–32PubMedCrossRefGoogle Scholar
  11. 11.
    Chapman SJ, Cookson WO, Musk AW, et al. Benign asbestos pleural diseases. Curr Opin Pulm Med 2003; 9(4): 266–71PubMedCrossRefGoogle Scholar
  12. 12.
    Singh N, Davis GS. Review: occupational and environmental lung disease. Curr Opin Pulm Med 2002; 8(2): 117–25PubMedCrossRefGoogle Scholar
  13. 13.
    Putz EF. Imaging bronchogenic carcinoma. Chest 2000; 117: 90S–5SCrossRefGoogle Scholar
  14. 14.
    Polansky SM, Ravin CE, Prosnitz LR. Pulmonary changes after primary irradiation for early breast carcinoma. Am J Roentgenol 1980; 134: 101–5Google Scholar
  15. 15.
    Morgan E, Baum E, Breslow N, et al. Chemotherapy-related toxicity in infants treated according to the Second National Wilms’ Tumour Study. J Clin Oncol 1988; 6: 51–5PubMedGoogle Scholar
  16. 16.
    Shapiro SJ, Shapiro SD, Mill WB, et al. Prospective study of long-term pulmonary manifestations of mantle irradiation. Int J Radiat Oncol Biol Phys 1990; 19: 707–14PubMedCrossRefGoogle Scholar
  17. 17.
    Morgan GW, Pharm B, Breit SN. Radiation and the lung: a reevaluation of the mechanisms of mediating pulmonary injury. Int J Radiat Oncol Biol Phys 1995; 31: 361–9PubMedCrossRefGoogle Scholar
  18. 18.
    Yamada M, Kudoh S, Hirata K, et al. Risk factors of pneumonitis following chemoradiotherapy for lung cancer. Eur J Cancer 1998; 34: 71–5PubMedCrossRefGoogle Scholar
  19. 19.
    Choi NC, Kanarek DJ. Toxicity of thoracic radiotherapy on pulmonary function in lung cancer. Lung Cancer 1994; 10Suppl. 1: S219–30PubMedCrossRefGoogle Scholar
  20. 20.
    Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer: adopted on May 16, 1997 by the American Society of Clinical Oncology. J Clin Oncol 1997; 15 (8): 2996–3018Google Scholar
  21. 21.
    Hara R, Itami J, Komiyama T, et al. Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after stereotactic radiotherapy for lung tumors. Chest 2004; 125(1): 340–4PubMedCrossRefGoogle Scholar
  22. 22.
    Ishii H, Mukae H, Kadota J, et al. High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia. Thorax 2003; 58: 52–7PubMedCrossRefGoogle Scholar
  23. 23.
    Fu X, Huang H, Bentel G, et al. Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biological parameters V30 and transforming growth factor β. Int J Radiat Oncol Biol Phys 2001; 50: 899–908PubMedCrossRefGoogle Scholar
  24. 24.
    Goto K, Kodama T, Sekine I, et al. Serum levels of KL-6 are useful biomarkers for severe radiation pneumonitis. Lung Cancer 2001; 34: 141–8PubMedCrossRefGoogle Scholar
  25. 25.
    Choi NC. Radioprotective effect of amifostine in radiation pneumonitis. Semin Oncol 2003; 30: 10–7PubMedCrossRefGoogle Scholar
  26. 26.
    Antonadou D, Petridis A, Synodinou M, et al. Amifostine reduces radiochemotherapy-induced toxicities in patients with locally advanced non-small cell lung cancer. Semin Oncol 2003; 30: 2–9PubMedCrossRefGoogle Scholar
  27. 27.
    Movsas B, Scott C, Langer C, et al. Phase III study of amifostine in patients with locally advanced non-small cell lung cancer receiving chemotherapy and hyperfractionated radiation (chemo/HFxRT): Radiation Therapy Oncology Group (RTOG) 98-01 [abstract]. Proc Am Soc Clin Oncol 2003; 22: 636Google Scholar
  28. 28.
    McCarty MJ, Lillis P, Vukelja SJ. Azathioprine as a steroidsparing agent in radiation pneumonitis. Chest 1996; 109: 1397–140PubMedCrossRefGoogle Scholar
  29. 29.
    Muroaka T, Badoh S, Fujita J. Corticosteroid refractory radiation pneumonitis that remarkably responded to cyclosporin A. Intern Med 2002; 41: 730–3CrossRefGoogle Scholar
  30. 30.
    Sleijfer S. Bleomycin-induced pneumonitis. Chest 2001; 120(2): 617–24PubMedCrossRefGoogle Scholar
  31. 31.
    Pearl M. Busulfan lung. Am J Dis Child 1977; 131: 650–2PubMedGoogle Scholar
  32. 32.
    Litman J, Dail D, Spitzer G. Early pulmonary toxicity after administration of high-dose BCNU. Cancer Treat Rep 1981; 65: 39–44Google Scholar
  33. 33.
    Mohr M, Kingreen D, Ruhl H, et al. Interstitial lung disease: an underdiagnosed side effect of chlorambucil? Ann Hematol 1993; 67: 305–7PubMedCrossRefGoogle Scholar
  34. 34.
    Cooper Jr JA, White DA, Matthay RA. Drug-induced pulmonary disease. 1: cytotoxic drugs. Am Rev Respir Dis 1986; 133: 321–40PubMedGoogle Scholar
  35. 35.
    Tham RT, Peters WG, de Bruine FT, et al. Pulmonary complications of cytosine-arabinoside therapy: radiographic findings. AJR Am J Roentgenol 1987; 149: 23–7PubMedGoogle Scholar
  36. 36.
    Read WL, Mortimer JE, Picus J. Severe interstitial pneumonitis associated with docetaxel administration. Cancer 2002; 94: 847–53PubMedCrossRefGoogle Scholar
  37. 37.
    Levin M, Aziz M, Opitz L. Steroid-responsive interstitial pneumonitis after fludarabine therapy. Chest 1997; 111: 1472–3PubMedCrossRefGoogle Scholar
  38. 38.
    Wong MK, Bjarnason GA, Hrushesky WJ, et al. Steroid-responsive interstitial lung disease in patients receiving 2′-deoxy-5- fluorouridine-infusion chemotherapy: report of 3 cases. Cancer 1995; 75: 2558–64PubMedCrossRefGoogle Scholar
  39. 39.
    Barlesi F, Villani P, Doddoli C, et al. Gemcitabine-induced severe pulmonary toxicity. Fundam Clin Pharmacol 2004; 18(1): 85–91PubMedCrossRefGoogle Scholar
  40. 40.
    Madarnas Y, Webster P, Shorter AM, et al. Irinotecan-associated pulmonary toxicity. Anticancer Drugs 2000; 11(9): 709–13PubMedCrossRefGoogle Scholar
  41. 41.
    Goucher G, Rowand V, Hawkins J. Melphalan-induced pulmonary interstitial fibrosis. Chest 1980; 77: 805–6PubMedCrossRefGoogle Scholar
  42. 42.
    Sostman H, Matthay R, Putman C, et al. Methotrexate-induced pneumonitis. Medicine (Baltimore) 1976; 55: 371–88CrossRefGoogle Scholar
  43. 43.
    Verweij J, van Zanten T, Souren T, et al. Prospective study on the dose relationship of mitomycin C-induced interstitial pneumonitis. Cancer 1987; 60: 756–61PubMedCrossRefGoogle Scholar
  44. 44.
    Taniguchi N, Shinagawa N, Kinoshita I, et al. A case of paclitaxel-induced pneumonitis. Nihon Kokyuki Gakkai Zasshi 2004; 42: 158–63PubMedGoogle Scholar
  45. 45.
    Brooks Jr BJ, Hendler NB, Alvarez S, et al. Delayed life-threatening pneumonitis secondary to procarbazine. Am J Clin Oncol 1990; 13: 244–6PubMedCrossRefGoogle Scholar
  46. 46.
    Furuse K, Kubota K, Kawahara M, et al. A phase II study of vinorelbine, a new derivative of vinca alkaloid, for previously untreated non-small cell lung cancer: Japan Vinorelbine Lung Cancer Study Group. Lung Cancer 1994; 11: 385–91PubMedCrossRefGoogle Scholar
  47. 47.
    Adamson IYR, Bowden DH. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol 1974; 77: 185–91PubMedGoogle Scholar
  48. 48.
    Dik WA, McAnulty RJ, Versnel MA, et al. Short course of dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats. Thorax 2003; 58: 765–71PubMedCrossRefGoogle Scholar
  49. 49.
    White DA, Stover DE. Severe bleomycin-induced pneumonitis: clinical features and response to corticosteroids. Chest 1984; 86: 723–8PubMedCrossRefGoogle Scholar
  50. 50.
    Nici L, Calabresi P. Amifostine modulation of bleomycin-induced lung injury in rodents. Semin Oncol 1999; 26: 28–33PubMedGoogle Scholar
  51. 51.
    Herman EH, Hasinoff BB, Zhang J, et al. Morphologic and morphometric evaluation of the effect of ICRF-187 on bleomycin-induced pulmonary toxicity. Toxicology 1995; 98: 163–75PubMedCrossRefGoogle Scholar
  52. 52.
    Lossos IS, Or R, Goldstein RH, et al. Amelioration of bleomycin-induced lymphokine production by cyclosporin A. Exp Lung Res 1996; 22: 337–49PubMedCrossRefGoogle Scholar
  53. 53.
    Punithavathi D, Venkatesan N, Babu M. Curcumin inhibition of bleomycin-induced pulmonary fibrosis in rats. Br J Pharmacol 2000; 131: 169–72PubMedCrossRefGoogle Scholar
  54. 54.
    Wang R, Ibarra-Sunga O, Verlinsli L, et al. Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor. Am J Physiol Lung Cell Mol Physiol 2000; 279: 143–51Google Scholar
  55. 55.
    Kuwano K, Kunitake R, Maeyama T, et al. Attenuation of bleomycin-induced pneumopathy in mice by a caspase inhibitor. Am J Physiol Lung Cell Mol Physiol 2001; 280: 316–25Google Scholar
  56. 56.
    Corbel M, Caulet-Maugendre S, Germain N, et al. Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat. J Pathol 2001; 193: 538–45PubMedCrossRefGoogle Scholar
  57. 57.
    Einhorn L, Krause M, Hornback N, et al. Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer. Cancer 1976; 37: 2414–6PubMedCrossRefGoogle Scholar
  58. 58.
    Cardenal F, Paz Lopez-Cabrenizo M, Anton A, et al. Randomised phase III study of gemcitabine plus cisplatin versus etoposide plus cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 1999; 17: 12–7PubMedGoogle Scholar
  59. 59.
    Sederholm C. Gemcitabine compared with gemcitabine plus carboplatin in advanced non-small cell lung cancer: a phase III study by the Swedish Lung Cancer Study Group [abstract]. Proc Am Soc Clin Oncol 2002; 21: 291Google Scholar
  60. 60.
    Roychowdhury DF, Cassidy CA, Peterson P, et al. A report on serious pulmonary toxicity associated with gemcitabine-based therapy. Invest New Drugs 2002; 20: 311–5PubMedCrossRefGoogle Scholar
  61. 61.
    Gemzar product monograph. Basingstoke: Eli Lilly and Company, 2003Google Scholar
  62. 62.
    Boiselle PM, Morrin MM, Huberman MS. Gemcitabine pulmonary toxicity: CT features. J Comput Assist Tomogr 2000; 24(6): 977–80PubMedCrossRefGoogle Scholar
  63. 63.
    Bergeron A, Bergot E, Vilela G, et al. Hypersensitivity pneumonitis related to imatinib mesylate. J Clin Oncol 2002; 20: 4271–2PubMedCrossRefGoogle Scholar
  64. 64.
    Ma CX, Hobday TJ, Jett JR. Imatinib mesylate-induced interstitial pneumonitis. Mayo Clin Proc 2003; 78(12): 1578–9PubMedCrossRefGoogle Scholar
  65. 65.
    Radzikowska E, Szczepulska E, Chabowski M, et al. Organising pneumonia caused by trastuzumab (herceptin) therapy for breast cancer. Eur Respir J 2003; 21: 552–5PubMedCrossRefGoogle Scholar
  66. 66.
    Tan AR, Yang X, Berman A, et al. Evaluation of epidermal growth factor receptor signaling in tumour and skin biopsies after treatment with OSI-774 in patients with metastatic breast cancer [abstract]. Proc Am Soc Clin Oncol 2003; 22: 196Google Scholar
  67. 67.
    Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999; 82: 241–50PubMedCrossRefGoogle Scholar
  68. 68.
    Volm M, Rittgen W, Drings P. Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. Br J Cancer 1998; 77: 663–9PubMedCrossRefGoogle Scholar
  69. 69.
    Pavelic K, Banjac Z, Pavelic J, et al. Evidence for a role of EGF receptor in the progression of human lung carcinoma. Anticancer Res 1993; 13: 1133–7PubMedGoogle Scholar
  70. 70.
    Fujino S, Enokibori T, Tezuka N, et al. A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. Eur J Cancer 1996; 32: 2070–4CrossRefGoogle Scholar
  71. 71.
    Meert AP, Martin B, Delmotte P, et al. The role of EGF-R expression on patient survival in lung cancer: a systemic review with meta-analysis. Eur Respir J 2002; 20(4): 975–81PubMedCrossRefGoogle Scholar
  72. 72.
    Wakeling AE, Guy SP, Woodburn JR, et al. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 2002; 62: 5749–54PubMedGoogle Scholar
  73. 73.
    Ranson M, Hammond LA, Ferry D, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well-tolerated and active in patients with solid, malignant tumours: results of a phase I trial. J Clin Oncol 2002; 20: 2240–50PubMedCrossRefGoogle Scholar
  74. 74.
    Herbst RS, Maddox AM, Rothenberg ML, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small cell lung cancer and other solid tumours: results of a phase I trial. J Clin Oncol 2002; 20: 3815–25PubMedCrossRefGoogle Scholar
  75. 75.
    Baselga J, Rischin D, Ranson M, et al. Phase I safety, pharmacokinetic and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor, in patients with five selected solid tumour types. J Clin Oncol 2002; 20: 4292–302PubMedCrossRefGoogle Scholar
  76. 76.
    Nagawaka K, Tamura T, Negoro S, et al. Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) in Japanese patients with solid malignant tumours. Ann Oncol 2003; 14: 922–30CrossRefGoogle Scholar
  77. 77.
    Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomised phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003; 21: 2237–46PubMedCrossRefGoogle Scholar
  78. 78.
    Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomised trial. JAMA 2003; 290: 2149–58PubMedCrossRefGoogle Scholar
  79. 79.
    Blackledge G, Averbuch S. Gefitinib (‘Iressa’, ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer 2004; 90: 566–72PubMedCrossRefGoogle Scholar
  80. 80.
    Cohen MH, Williams GA, Sridhara R, et al. FDA drug approval summary: gefitinib (ZD1839; Iressa) tablets. Oncologist 2003; 8: 303–6PubMedCrossRefGoogle Scholar
  81. 81.
    Gonzalez-Larriba JL, Giaccone G, van Oosterom A, et al. ZD1839 (‘Iressa’) in combination with gemcitabine and cisplatin in chemonaive patients with advanced solid tumours: final results of a phase I trial [abstract]. Proc Am Soc Clin Oncol 2002; 21: 95Google Scholar
  82. 82.
    Miller VA, Johnson DH, Krug LM, et al. Pilot trial of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib plus carboplatin and paclitaxel in patients with stage IIIb or IV non-small-cell lung cancer. J Clin Oncol 2003; 21: 2094–100PubMedCrossRefGoogle Scholar
  83. 83.
    Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small cell lung cancer: a phase III trial — INTACT 1. J Clin Oncol 2004; 22: 777–84PubMedCrossRefGoogle Scholar
  84. 84.
    Herbst RS, Giaccone G, Schiller JH, et al. Gemcitabine in combination with paclitaxel and carboplatin in advanced nonsmall cell lung cancer: a phase III trial — INTACT 2. J Clin Oncol 2004; 22: 785–94PubMedCrossRefGoogle Scholar
  85. 85.
    Scagliotti G, Rossi A, Novello S, et al. Gefitinib (ZD1839) combined with gemcitabine or vinorelbine as single agent in elderly patients with advanced non-small cell lung cancer [abstract]. Proc Am Soc Clin Oncol 2004; 23: 633Google Scholar
  86. 86.
    Gatzemeier U, Pluzanska A, Szcesna A, et al. Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine chemotherapy in advanced non-small cell lung cancer [abstract]. Proc Am Soc Clin Oncol 2004; 23: 617Google Scholar
  87. 87.
    Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase III trial of erlotinib HCl (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small cell lung cancer [abstract]. Proc Am Soc Clin Oncol 2004; 23: 617Google Scholar
  88. 88.
    Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304(5676): 1497–500PubMedCrossRefGoogle Scholar
  89. 89.
    Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129–39PubMedCrossRefGoogle Scholar
  90. 90.
    Sumpter K, Harper-Wynne C, O’Brien M. Severe acute interstitial pneumonia and gefitinib. Lung Cancer 2003; 43: 367–8CrossRefGoogle Scholar
  91. 91.
    Madtes DK, Busby HK, Strandjord TP, et al. Expression of transforming growth factor-alpha and epidermal growth factor receptor is increased following bleomycin-induced lung injury in rats. Am J Respir Cell Mol Biol 1994; 11: 540–1PubMedGoogle Scholar
  92. 92.
    Suzuki H, Aoshiba K, Yokohori N, et al. Epidermal growth factor receptor tyrosine kinase inhibition augments a murine model of pulmonary fibrosis. Cancer Res 2003; 63: 5054–9PubMedGoogle Scholar
  93. 93.
    AstraZeneca and Iressa Expert Committee. Final report on interstitial lung disease (ILD) related to gefitinib (Iressa® tablet 250), 2003Google Scholar
  94. 94.
    Forsythe B, Faulkner K. Clinical experience with gefitinib (‘Iressa’, ZD1839): an overview of safety and tolerability. Lung Cancer 2003; 41Suppl. 2: S70–1CrossRefGoogle Scholar
  95. 95.
    Hotta K, Harita S, Bessho A, et al. Interstitial lung disease during gefitinib treatment in Japanese patients with non-small cell lung cancer: Okayama Lung Cancer Study Group [abstract]. Proc Am Soc Clin Oncol 2004; 23: 629Google Scholar
  96. 96.
    Seto T, Yamamoto N. Interstitial lung disease induced by gefitinib in patients with advanced non-small cell lung cancer: results of a West Japan Thoracic Oncology Group epidemiological survey [abstract]. Proc Am Soc Clin Oncol 2004; 23: 629Google Scholar
  97. 97.
    Iressa product monograph. London: AstraZeneca, 2003Google Scholar
  98. 98.
    Richardson CM, Sharma RA, Cox G, et al. Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer: potential targets for chemoprevention and systemic therapy. Lung Cancer 2003; 39: 1–13PubMedCrossRefGoogle Scholar
  99. 99.
    Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Sarah Danson
    • 1
  • Fiona Blackhall
    • 1
  • Paul Hulse
    • 2
  • Malcolm Ranson
    • 1
  1. 1.Department of Medical OncologyChristie Hospital NHS TrustWithingtonUK
  2. 2.Department of RadiologyChristie Hospital NHS TrustWithingtonUK

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