Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Introduction

This article has been updated

Globally, lung cancer is the leading cause of cancer-related mortality in both men and women (Ferlay et al, 2000), with non-small-cell lung cancer (NSCLC) accounting for 80% of these cases. Many patients present with advanced/metastatic disease. Despite aggressive surgical or chemotherapeutic intervention, the prognosis of patients diagnosed with NSCLC remains poor, with an overall cure rate of <15% (Sridhar et al, 2003). Therefore, new safe and effective treatments for NSCLC are urgently needed.

Aberrant cell signalling by receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) is known to play a critical role in the development and progression of cancer (Ullrich et al, 1984; Zwick et al, 2001). The EGFR pathway is highly expressed in a variety of solid tumours, including NSCLC, and has been implicated in tumorigenesis through its effects upon cell-cycle progression, apoptosis, angiogenesis, tumour-cell motility and metastasis (Ciardiello and Tortora, 2001; Salomon and Gullick, 2001; Arteaga, 2002; Bunn Jr and Franklin, 2002). As EGFR expression correlates with poor prognosis, disease progression and resistance to chemotherapy (Baselga, 2002; Wells, 2000), it has been identified as a potential therapeutic target in the treatment of cancer.

Gefitinib (‘Iressa’, ZD1839) is the first of a new class of EGFR tyrosine kinase inhibitors and, as such, physicians and patients are taking a great interest in its clinical profile and development. Two Phase II monotherapy trials (‘Iressa’ Dose Evaluation in Advanced Lung cancer (IDEAL) 1 and 2) have reported unprecedented antitumour activity and symptom relief in pretreated patients with advanced/metastatic NSCLC (Fukuoka et al, 2003); approximately 40% of patients experienced objective responses and stable disease accompanied by improvement in disease-related symptoms and 30% of patients survived for 1 year. The IDEAL trials underpinned the current use of gefitinib in clinical practice and, as of September 2003, gefitinib had been administered to approximately 90 000 patients worldwide. The only FDA-approved option for use in patients with NSCLC that has failed both platinum-based and docetaxel chemotherapy in the USA, gefitinib is also approved for use in previously treated patients in several other countries, including Japan and Australia. Our thirst for new knowledge of how best to use this novel targeted agent remains unquenched, and data from the real-life use of gefitinib can provide invaluable insight into the clinical application of gefitinib in a wide variety of settings.

The ‘Iressa’ Expanded Access Programme (EAP) enables patients to receive 250 mg day−1 gefitinib if they are ineligible for clinical trials or have no other treatment options available. To date (September 2003), approximately 40 000 generally heavily pretreated patients with advanced NSCLC, in 73 countries, have received gefitinib on a compassionate-use basis via the EAP. Thus, the EAP provides a wealth of real-life experience of using gefitinib in elderly patients, patients with poor performance status and those with brain metastases. It is important that the experience of using gefitinib in the EAP is shared between all physicians who are striving to provide the best level of care for their patients, including those who are not necessarily part of the EAP.

In June 2003, the ‘Iressa’ Clinical Experience (ICE) meeting was held in Madrid, Spain, and provided a unique opportunity for 150 EAP investigators to disseminate the real-life experience of gefitinib generated through EAP usage. The sharing of case reports and series by EAP physicians generated an overall (rather than individual) perception of the efficacy, safety and quality-of-life impact of gefitinib. Unique insights into the clinical use of gefitinib were gained from the meeting, some of them unexpected. In order to disseminate this knowledge to all physicians, the data presented at the ICE meeting have been used to describe the concept of assessing clinical benefit, the tolerability, the treatment of patients with brain metastases and the treatment of elderly and unfit patients, using gefitinib in a real-life setting. These data will provide physicians with invaluable insight into the clinical application of gefitinib in a wide variety of settings, and enable them to provide the best level of care for their patients.

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  1. Arteaga C (2002) Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. Semin Oncol 29: 3–9

    CAS  Article  Google Scholar 

  2. Baselga J (2002) Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 7(Suppl 4): 2–8

    CAS  Article  Google Scholar 

  3. Bunn Jr P, Franklin W (2002) Epidermal growth factor receptor expression, signal pathway, and inhibitors in non-small-cell lung cancer. Semin Oncol 29: 38–44

    CAS  Article  Google Scholar 

  4. Ciardiello F, Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7: 2958–2970

    CAS  Google Scholar 

  5. Ferlay J, Bray F, Pisani P, Parkin DM (2000) GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide, version 1.0, IARC Cancer Base No. 5. Limited version available from http://www-dep.iarc.fr/globocan/globocan.html Last updated 03/02/2001, Lyon: IARC Press

    Google Scholar 

  6. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard J-Y, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong R-P, Baselga J (2003) Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 21: 2237–2246

    CAS  Article  Google Scholar 

  7. Salomon D, Gullick W (2001) The erbB family of receptors and their ligands: multiple targets for therapy. Signal 2: 4–11

    Google Scholar 

  8. Sridhar SS, Seymour L, Shepherd FA (2003) Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell-lung cancer. Lancet Oncol 4: 397–406

    CAS  Article  Google Scholar 

  9. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J (1984) Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 309: 418–425

    CAS  Article  Google Scholar 

  10. Wells A (2000) The epidermal growth factor receptor (EGFR) – a new target in cancer therapy. Signal 1: 4–11

    Google Scholar 

  11. Zwick E, Bange J, Ullrich A (2001) Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr Relat Cancer 8: 161–173

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to U Gatzemeier.

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and Permissions

About this article

Cite this article

Gatzemeier, U. Introduction. Br J Cancer 89, S1–S2 (2003). https://doi.org/10.1038/sj.bjc.6601475

Download citation

Search

Quick links