A systematic overview of chemotherapy effects in non-small cell lung cancer

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on chemotherapy for non-small cell lung cancer (NSCLC) is based on 53 scientific publications including six meta-analyses based on 65 prospective randomised trials comprising 15,607 patients and an additional 32 prospective randomised studies including 8,902 patients. The conclusions reached can be summarised into the following points: In stage IIIB-IV disease, published data demonstrate that cisplatin-based chemotherapy confers a modest, median 1.5-3 months, prolongation of survival. The closely related compound carboplatin seems to provide similar effects. Randomised studies indicate symptomatic relief and improvement of indices of quality of life (QoL) for patients who receive platinum-based combination chemotherapy or single drug therapy with more recent compounds. Data supporting the use of chemotherapy are not available for patients in poor general condition (WHO performance status 3 4) and evidence is limited for elderly patients (above 70-75 years). Platinum-based chemotherapy can be recommended for selective use in routine care of advanced NSCLC although patients should be encouraged to participate in controlled clinical trials to further elucidate the role of chemotherapy in advanced disease. In advanced disease, recent data suggest that the newer agents gemcitabine, paclitaxel, irinotecan and vinorelbine, in combination with cisplatin, provide an additional survival benefit compared with earlier cisplatin-based regimens. Furthermore, paclitaxel, docetaxel and vinorelbine as single agents seemingly provide a survival benefit over supportive care alone comparable to that of older cisplatin-based combinations. A standard regimen for advanced disease cannot yet be defined. Until more data are at hand, it is recommended to be platinum-based and preferably combined with one of the newer agents. At progression after platinum-based chemotherapy for advanced disease, limited data indicate a small survival benefit from docetaxel over supportive care alone. Such second-line chemotherapy of advanced disease can be recommended for selected patients but should preferably be confined to controlled clinical trials. In stage III disease, published data show that induction cisplatin-based chemotherapy before radical radiotherapy modestly prolongs long-term survival and lowers the incidence of distant metastases compared with radiotherapy alone. Furthermore, published data show that concurrent chemo- and radiotherapy with cisplatin or carboplatin may enhance local control and long-term survival. Chemotherapy in this setting can be recommended for selected patients but treatment should preferably be given within a controlled clinical trial. In stage IIIAN2 disease, data from pilot studies demonstrate that surgery after induction chemotherapy is feasible. Pathologically complete remissions have been confirmed in 10-20% of treated patients. Two small randomised studies demonstrate a significant survival advantage for induction chemotherapy followed by surgery compared with surgery alone. Induction chemotherapy can be recommended for selected patients but treatment should preferably be given within a controlled clinical trial. The superiority of induction chemotherapy plus surgery compared with combined chemotherapy and radical irradiation has not been proven in a randomised trial but currently such studies are under way. In the adjuvant setting, published data suggest that cisplatin-based chemotherapy after radical surgery may increase five-year survival from around 50% by a further 5% but the confidence interval for this estimate is too wide for firm conclusions. Large-scale prospective randomised trials are under way to resolve this important issue and adjuvant chemotherapy is, thus, not recommended for routine treatment.