Chemotherapy for advanced non-small-cell lung cancer

Abstract

Patients with lung cancer currently have a poor prognosis. In 1991 in England and Wales alone, 34 190 people died from the disease, and since 70 to 80% of lung cancer cases are histopathologically of the non small cell (NSCLC) type, NSCLC remains the leading cause of cancer deaths in the U.K. with mortality rates exceeding 90% of the incidence. The best chance of a cure is a surgical resection, but this is only appropriate for patients with early stage disease (Stage I, II and a few Stage I l i a patients). Unfortunately, since symptoms rarely present until later stages of the disease, the majority of patients are unsuitable for a resection. Therefore it would appear that effort directed at improving early diagnosis might impact survival but several studies (1,2) using either screening, chest X-rays or sputum cytology have failed to demonstrate the usefulness of this approach (1,2). No difference in survival outcome between the unscreened and screened groups was observed with little evidence for a stage shift between the two groups. In Britain about 65% of patients are inoperable at presentation and at exploratory thoracotomy a further 15% are found to be unresectable. For those patients whose tumours are not resectable, the curative treatment options are perceived as being limited. Perhaps as a result of this perception, only 40% of all lung cancer patients are referred to a medical oncologist or radiotherapist in the U.K. (3). However, despite this nihilism radical radiotherapy with curative intent can be effective in prolonging life when given on its own (4) but again, is appropriate for only a minority of patients (4). Therefore the vast majority of patients currently have no prospect of cure. Chemotherapy probably represents the best chance for an improved outcome in these patients. However, the role of chemotherapy in the treatment of NSCLC in the U K remains largely experimental. This is partially due to the morbidity associated with the use of traditional chemotherapeutic agents and the marginal impact on survival. Nevertheless there is emerging evidence of a small but significant impact on survival with cisplatin based polychemotherapy regimens. Even though the effect is small this is an important finding given the prevalence of the disease. In addition, it is encouraging to note the identification of several novel chemotherapeutic drugs with efficacy in advanced NSCLC. Their usefulness, either as single agents or in combination, must be substantiated in the context of large randomized clinical trials. Indeed, it needs to be recognized that further advances can only be made by the inclusion of patients into well designed and controlled clinical trials. Whilst such studies are widely quoted as having an impact on clinical practice, it is sobering to reflect that a recent survey (3) of U.K. clinical practice suggested that fewer than 5% of lung cancer patients are currently treated in a clinical trial. In the current absence of potential for cure, another key outcome in this group of patients is symptom palliation. It is well recognized that effective palliation of symptoms due to intrathoracic disease may be achieved with the use of radiotherapy. Several important studies have addressed the question as to how many fractions of radiotherapy are needed to give adequate symptom relief (5,6). In a recent review (7) it was suggested the chemotherapy is effective in symptom palliation and should be offered to selected patients. These interesting new developments in the chemotherapy of advanced NSCLC are the subject of this review and mean that it is now time to consider whether the therapeutic nihilism, so long associated with the treatment of advanced NSCLC, is still justified.