Inhibition of Epidermal Growth Factor Receptor and Symptom Improvement in Advanced Non-Small Cell Lung Cancer

The majority of patients with non-small cell lung cancer (NSCLC) are not candidates for curative resection because of advanced disease at the time of diagnosis. Systemic chemotherapy has been employed with modest success to provide symptom relief and prolonged survival for patients with this incurable disease. Any benefit derived from chemotherapy in this palliative setting must be balanced against the substantial toxicity associated with cytotoxic drugs. A novel approach to anticancer treatment based on specific targeting molecular processes has recently demonstrated efficacy. ZD1839 is a low-molecular-weight molecule that is capable of inhibiting epidermal growth factor receptor (EGFR)-associated tyrosine kinase activity. Consequently, ZD1839 interrupts EGFR-mediated activities such as tumor cellular proliferation, motility, survival, and invasiveness. In vitro and in vivo studies have shown that ZD1839 has activity against NSCLC. The results of ZD1839 in randomized clinical trials of patients with advanced NSCLC are reported in this review. In addition to evaluating response rates and clinical endpoints, these trials prospectively evaluated symptom improvement and quality of life.

Non-small cell lung cancer (NSCLC) - symptom control - quality of life - ZD1839

REFERENCES

• 1 Cancer Facts & Figures-2004. Atlanta, GA; American Cancer Society 2004 4
• 2 Johnson D H. Locally advanced, unresectable non-small cell lung cancer: new treatment strategies.  Chest. 2000;  117 123S-126S
• 3 Non-small Cell Lung Cancer Collaborative Group . Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials.  BMJ. 1995;  311 899-909
• 4 Beretta G, Michetti G, Belometti M et al.. Gemcitabine plus vinorelbine in elderly or unfit patients with non-small-cell lung cancer.  Br J Cancer. 2000;  83 573-576
• 5 Gridelli C, Cigolari S, Gallo C et al.. Activity and toxicity of gemcitabine and gemcitabine + vinorelbine in advanced non-small-cell lung cancer elderly patients: phase II data from the Multicenter Italian Lung Cancer in the Elderly Study (MILES) randomized trial.  Lung Cancer. 2001;  31 277-284
• 6 Cella D F, Eton D T, Fairclough D L et al.. What is a clinically meaningful change on the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire? Results from Eastern Cooperative Oncology Group (ECOG) Study 5592.  J Clin Epidemiol. 2002;  55 285-295
• 7 Cella D F, Bonomi A E, Lloyd S R et al.. Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument.  Lung Cancer. 1995;  12 199-220
• 8 Franklin W A, Veve R, Hirsch F R et al.. Epidermal growth factor receptor family in lung cancer and premalignancy.  Semin Oncol. 2002;  29 3-14
• 9 Arteaga C L, Khuri D, Krystal G et al.. Overview of rationale and clinical trials with signal transduction inhibitors in lung cancer.  Semin Oncol. 2002;  29 15-26
• 10 Ranson M, Hammond L A, 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 tumors: results of a phase I trial.  J Clin Oncol. 2002;  20 2240-2250
• 11 Raben D, Helfrich B A, Chan D et al.. ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer.  Semin Oncol. 2002;  29 37-46
• 12 Kris M G, Natale R B, Herbst R S et al.. A phase II trial of ZD1839 (“Iressa”) in advanced non-small cell lung cancer (NSCLC) patients who had failed platinum- and docetaxel-based regimens (IDEAL 2) [abstract 1166].  Proc Am Soc Clin Oncol. 2002;  21 292a
• 13 Fukuoka M, Yano S, Giaccone G et al.. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer.  J Clin Oncol. 2003;  21 2237-2246
• 14 Douillard J-Y, Giaccone G, Horai T et al.. Improvement in disease-related symptoms and quality of life in patients with advanced non-small-cell lung cancer (NSCLC) treated with ZD1839 (“Iressa”) (IDEAL 1) [abstract 1195].  Proc Am Soc Clin Oncol. 2002;  21 299a
• 15 Natale R B, Skarin A T, Maddox A-M et al.. Improvement in symptoms and quality of life for advanced non-small-cell lung cancer patients receiving ZD1839 (“Iressa”) in IDEAL 2 [abstract 1167].  Proc Am Soc Clin Oncol. 2002;  21 292a
• 16 Cella D. Impact of ZD1839 on non-small cell lung cancer-related symptoms as measured by the Functional Assessment of Cancer Therapy-Lung Scale.  Semin Oncol. 2003;  30(suppl 1) S39-S48
• 17 Shepherd F A. Chemotherapy for non-small cell lung cancer: have we reached a new plateau?.  Semin Oncol. 1999;  26(suppl 4) S3-S11
• 18 Giaccone G. Targeted therapy in non-small cell lung cancer.  Lung Cancer. 2002;  38(suppl 2) S29-S32
• 19 Natale R B, Zaretsky S L. ZD1839 (Iressa): what's in it for the patient?.  Oncologist. 2002;  7(suppl 4) S25-S30