Clinical studies in non-small cell lung cancer: the CALGB experience

Since 1984, the Cancer and Leukemia Group B (CALGB) has focused its clinical research in stage IV non-small cell lung cancer (NSCLC) on investigations of new agents and combinations. Currently, efforts are aimed at identifying non-cisplatin-based combinations with an increased therapeutic index. In stage III disease multimodality therapies have been pursued. Dillman et al. reported a study comparing standard radiotherapy versus induction chemotherapy followed by radiotherapy in patients 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 months) 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 locoregionally advanced NSCLC. In a subsequent study, the administration of additional "posterior" chemotherapy was not found to be feasible because of early disease progression and toxicity, while the administration 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 cycles of cisplatin and vinblastine followed by radiotherapy with an experimental arm of cisplatin and vinblastine followed by radiotherapy and concomitant carboplatin. Accrual to this study has been completed and results are expected in the near future. In resectable stage III disease, studies have focused on the optimal sequencing of multimodality therapy. A randomized study comparing standard regional therapy with radiotherapy 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 paclitaxel, gemcitabine, and vinorelbine in combination with cisplatin in the induction setting and as concomitant chemoradiotherapy has recently been activated.