Treatment of non-small-cell lung cancer: a perspective on the recent advances and the experience with gefitinib

Abstract

Worldwide, non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related mortality and, until screening detects early disease, treatment for the majority of patients will consist of radiation therapy, chemotherapy or combinations thereof. Modern mono and doublet chemotherapy regimens have translated into modest increases in life expectancy and improved quality of life, but at the expense of systemic and pulmonary adverse events (AEs). There is a great unmet need to provide effective therapy for advanced NSCLC that does not have the toxicity burden of conventional chemotherapy and radiotherapy. Novel drugs that inhibit a range of growth factor receptors, such as the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib ('Iressa') and erlotinib ('Tarceva') or the monoclonal antibody cetuximab ('Erbitux'), have recently been evaluated. Having demonstrated antitumour activity and rapid symptom improvement in pretreated patients with advanced NSCLC, gefitinib was approved in the USA, Japan and other countries. Gefitinib is well tolerated with a low incidence of grade 3/4 AEs. Interstitial lung disease has been reported in a small number of patients receiving gefitinib, although this may be attributed to other treatments and conditions. Nevertheless, although the use of novel treatments requires vigilance for unexpected AEs such as pulmonary toxicity, in this area of high unmet clinical need, the benefits outweigh the risks in patients for whom no other proven effective treatment exists.

Figure 1

Survival of patients with stage IV NSCLC receiving four different platinum-based combination chemotherapy regimens (Schiller et al, 2002). Reprinted with permission from: Schiller et al (2002). Copyright © 2002 Massachusetts Medical Society. All rights reserved.

Figure 2

Median overall survival time for each line of treatment (Massarelli et al, 2003). Reprinted from: Massarelli et al (2003). Copyright (2003), with permission from Elsevier.

Figure 3

Four-Arm Cooperative Study for advanced NSCLC in Japan: trial design.