CLINICAL-STUDIES IN NONSMALL CELL LUNG-CANCER - THE CALGB EXPERIENCE

Since 1984, the Cancer and Leukemia Group B (CALGB) has focused its cl inical research in stage IV non-small cell lung cancer (NSCLC) on inve stigations of new agents and combinations. Currently, efforts are aime d at identifying non-cisplatin-based combinations with an increased th erapeutic index. In stage III disease multimodality therapies have bee n pursued. Dillman et al. reported a study comparing standard radiothe rapy versus induction chemotherapy followed by radiotherapy in patient s with unresectable stage III NSCLC. The chemotherapy-treated patients were found to benefit with a 4-month increase in median survival time compared with patients receiving radiotherapy alone (13.8 vs. 9.7 mon ths) and an increased 3-year survival rate of 23% versus 11%. This was the first randomized cooperative group study demonstrating a survival advantage resulting from the use of induction chemotherapy in locoreg ionally advanced NSCLC. In a subsequent study, the administration of a dditional ''posterior'' chemotherapy was not found to be feasible beca use of early disease progression and toxicity, while the administratio n of induction chemotherapy followed by concomitant chemoradiotherapy was feasible; therefore, the latter approach was studied further in a randomized phase III setting. This study compared a standard of two cy cles of cisplatin and vinblastine followed by radiotherapy with an exp erimental arm of cisplatin and vinblastine followed by radiotherapy an d concomitant carboplatin. Accural to this study has been completed an d results are expected in the near future. In resectable stage III dis ease, studies have focused on the optimal sequencing of multimodality therapy. A randomized study comparing standard regional therapy with r adiotherapy and surgery versus a previously piloted approach combining chemotherapy, surgery, and radiotherapy was closed prematurely due to poor accrual. The next generation of studies in stage III NSCLC will focus on the integration of new chemotherapy agents into the treatment armamentarium for NSCLC. A randomized phase II study investigating pa clitaxel, gemcitabine, and vinorelbine in combination with cisplatin i n the induction setting and as concomitant chemoradiotherapy has recen tly been activated.