Docetaxel as neo-adjuvant therapy for radically treatable stage III non-small cell lung cancer: early results of an international phase III study

Abstract

During the last decade, neo-adjuvant chemotherapy has shown the potential to improve the survival of patients with stage III non-small cell lung cancer (NSCLC) [1–3]. A meta-analysis performed by the Non-small Cell Lung Cancer Collaborative Group has demonstrated a small survival advantage for patients who had received cisplatin-based neo-adjuvant therapy before definitive radical radiotherapy [4]. In this analysis, neo-adjuvant therapy was associated with a 13% reduction in mortality and a 5% increase in 5-year survival. There is a clear rationale for using neo-adjuvant chemotherapy before definitive local treatment of NSCLC by improving delivery of the chemotherapeutic agent to the tumour site through an intact blood supply that has not been disrupted by prior surgery or radiotherapy. Initially unresectable tumours may be transformed into operable ones, and the frequent occult extra-thoracic micrometastases in patients with stage III NSCLC may be eradicated. This approach may also reduce the extent of surgical resection and improve the degree of local control achieved with radiotherapy. The significant toxicity associated with cisplatin has led to the evaluation of other agents, including docetaxel, for the neo-adjuvant treatment of NSCLC. Single-agent docetaxel has been shown to be active in NSCLC. Four phase II trials, involving a total of 180 patients with advanced or metastatic NSCLC, have demonstrated that first-line therapy with docetaxel is associated with an objective overall response rate of 30% and a median overall survival of 9 months [5–8]. Docetaxel is one of the several chemotherapeutic agents that have recently received approval, in the USA and Europe, for second-line treatment of locally advanced or metastatic NSCLC. In view of its encouraging activity in advanced NSCLC, docetaxel is currently being investigated in the neo-adjuvant setting.