Between 170-250 patients per year were enrolled on lung cancer treatment trials between January, 1996, and December, 1999. Additionally, 200 patients were enrolled on ancillary trials, as well as quality of life and cancer control trials. During this grant cycle, we have published 11 abstracts and 12 manuscripts related to NCCTG trials. Six other manuscripts are in preparations. Three major accomplishments were made over this period: First, we have complete two phase III randomized trials with combined modality therapy that have evaluated the role of twice daily hyperfractionated radiotherapy. In these trails, patients received concurrent chemoradiotherapy. One trail was in small cell (SCLC) and the second in non-small cell lung cancer (NSCLC). These were important trials for scientifically evaluating hyperfractionated radiotherapy. Additionally, these trials further evaluated the evaluated the risks and benefits of concurrent chemoradiotherapy. We have learned that acutely concurrent therapy is somewhat more toxic, but tolerable, and results in improved survival for small cell lung cancer. However, hyperfractionated radiotherapy, when given with cycle 4 of chemotherapy, did not impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the impact on survival versus concurrent chemoradiotherapy with once a day irradiation. The results of the non- small cell lung cancer trial are pending. The small cell trial has resulted in a change in practice in the community with concurrent therapy becoming the standard. Second, our community-based oncologists and thoracic surgeons have successfully completed a neoadjuvant chemotherapy trial in early stage (stage I and II) lung cancer and participated in an adjuvant trial for resected stage II and IIIA non-small lung cancer. We have learned that neoadjuvant chemotherapy does not increase surgical morbidity and/or mortality. These trials have prepared us for participation in the current neoadjuvant phase III Intergroup trial (S9900) in early stage patients and Intergroup adjuvant trials in totally resected patients with more advanced disease. Third, new chemotherapy gents and combinations (LU103793, topotecan/paclitaxel topotecan/cisplatin) were tested in NSCLC and found not to be effective or associated with excessive toxicity. These are important negative findings. Additionally, topotecan/paclitaxel alternating with etoposide/cisplatin has been tested against small cell lung cancer with promising results. NCCTG was also a major contributor to the Intergroup surgical adjuvant trial for resected stage II/IIIA NSCLC (INT 0115). Future Plans. A new leadership team is now in place, and the group is focused on building on its strengths to advance the treatment of lung cancer. Accrual on phase III trials has not been adequate to conduct Phase III trials sorely within NCCTG in a timely fashion. Treatment trials within NCCTG in the next grant cycle will, therefore, be primarily phase II studies testing the role of novel chemotherapy agents and agents that will, therefore, be primarily phase II studies testing the role of novel chemotherapy agents and agents will target specific abnormalities. We will focus on novel agents that affect signal transduction pathways. Promising treatments will be brought forth for rapid testing in large phase III studies in the Intergroup setting. In addition to selected ancillary studies with treatment trials, translational research in the genetic epidemiology of lung cancer will be an area of emphasis. The third area of research will be the treatment of lung cancer in the elderly, who are increasingly represented in our patient population.