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Lung cancer is the most lethal cancer in men and women in the western world. Eighty per cent of cases are non-small-cell lung carcinoma (NSCLC) whose subtypes include squamous cell carcinoma, adenocarcinoma and large-cell carcinoma. Of these, approximately 80% will present with either locally advanced or metastatic disease – i.e. stage IIIB or IV disease – and are unlikely to be cured.
Treatment options for these patients include best supportive care (BSC), chemotherapy or a combination of radiotherapy and chemotherapy. NSCLC are less chemosensitive than small-cell carcinoma and complete responses are rare, but nevertheless chemotherapy provides some improvements in quality of life (QoL) and life expectancy compared with BSC, particularly in better performance status (PS) patients. This article will discuss the medical treatment of NSCLC, with some attention to the newer epidermal growth factor (EGFR) antagonists.
Chemotherapy versus Best Supportive Care
Chemotherapy became a serious entity for NSCLC only in the mid- 1990s, particularly after a meta-analysis by the Non-small Cell Lung Cancer Collaborative Group who looked at all randomised controlled trials (RCTs) of chemotherapy or BSC in all treatment situations (i.e. surgery, radiotherapy or BSC).1 In trials of chemotherapy versus BSC in advanced disease, nine RCTs showed that chemotherapy conferred a small survival advantage of six to eight weeks. However, in these retrospective analyses there were no QoL data. Chemotherapy regimes may have considerable side effects, thus it is important to take this into account. A balance will inevitably have to be struck between QoL and the effects of chemotherapy, which may be influenced by any additional morbidity of these regimes. After chemotherapy, overall one-year survival in advanced disease was 30% compared with BSC, where oneyear survival was only 17%.
The NSCLC Collaborative Group meta-analysis showed that only cisplatincontaining regimens were effective, but the advantages were small.1 Although a number of different regimens of these second-generation compounds have been used, there is little to choose between them.
However, several drugs in combination were better than single-agent therapy, with better response rates and prolonged survival, at the cost of increased toxicity with combination therapy. Common secondgeneration chemotherapy regimens include mitomycin, ifosfamide and cisplatin (MIC) and mitomycin, vinblastine and cisplatin (MVP). The effect of MIC versus BSC was studied by Cullen (1999) in 351 patients, demonstrating a prolongation in median survival of seven weeks.2 Smith et al. studied the effect of another common regime, and in particular the duration of chemotherapy, by administering either three or six cycles of MVP.3 The authors concluded that there was no benefit in continuing chemotherapy beyond three cycles in terms of median survival, one-year survival and QoL. These regimes were used in over 70% of the patients in the Big Lung trial, which compared BSC with four different chemotherapy regimes and importantly demonstrated a survival benefit with no detrimental effect in terms of QoL for the addition of chemotherapy.4 This advantage had been hinted at, for example, by Cullen et al., who compared four courses of MIC with BSC and demonstrated an increase in median survival of two months.2 The overall response rate to chemotherapy was 31%, with a complete response of 2% and a partial response of 29%. Only a small subset of patients entered a QoL study and this showed an improvement in the symptom scores as measured by the European Organisation for Research and Treatment of Cancer (EORTC QLC-LC13). However, the largest study of this type was the Big Lung trial, with nearly 400 patients recording QoL.