Therapies in Metastatic Non-small-cell Lung Carcinoma

European Oncology, 2008;4(2):31-3 DOI:


Lung cancer is the most common killing 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 is 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 and briefly consider the newer epidermal growth factor receptor (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 NSCLC Collaborative Group that 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 and chemotherapy regimes may have considerable side effects, both of which are important to take into account. Inevitably, there will be a balance between the effects of chemotherapy and response on QOL, which may be balanced by any additional morbidity of these regimes. After chemotherapy, the overall one-year survival rate in advanced disease was 30% compared with only 17% after BSC.

Chemotherapy Regimens
The NSCLC Collaborative Group meta-analysis showed that only cisplatin-containing regimens were effective, but the advantages were small.1 Although a number of different regimens of these secondgeneration 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 second-generation chemotherapy regimens include mitomycin, ifosfamide and cisplatin (MIC) and mitomycin, vinblastine and cisplatin (MVP). The effect of MIC versus BSC was studied by Cullen 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 that compared BSC with four different chemotherapy regimes. Importantly, it demonstrated a survival benefit with no detrimental effect in terms of QOL for the addition of chemotherapy.4