Future directions in non-small cell lung cancer. A personal view

At the 1991 6th World Conference on Lung Cancer sponsored by IASLC and held in Melbourne, the Future Directions summary described several critical clinical trials that were underway, reviewed the progress in cellular and molecular biology and decried the excessive nihilism and pessimism then rampant. The theme today is identical, but the baseline has advanced significantly. There is now a clear consensus that combined modality therapy is superior to single modality therapy for locally advanced NSCLC. The issues for future clinical trials are related to increasing the effectiveness of regimens known to be active in reducing toxicity. Radiation alone for Stage IIIB NSCLC and surgery alone for Stage IIIA NSCLC need not serve as control arms. The availability of several new, and significantly more active, chemotherapeutic compounds will drive the clinical trials in this arena for several years. Meta-analyses also demonstrate a clear benefit for chemotherapy over supportive care and only in the area of post-operative adjuvant therapy for resected NSCLC is the efficacy of therapy still in question. Our comprehension of the number and sequence of genetic mutations leading to clinical cancer is rapidly growing, although it is not likely that attempts to reverse specific mutations will lead to successful therapy for established tumors. On the other hand, early detection and prevention are becoming very real possibilities. Knowledge of specific mutations and the development of pharmacologic approaches to overcome them is the next area for clinical development. Optimism remains an appropriate response to developments in the area of NSCLC.