Novel Approaches in Stage III NSCLC
Presenter: Hak Choy, MD
Affiliation: Vanderbilt University School of Medicine
The top cause of cancer-related mortality in the United States among both males and females remains lung cancer. Typically, as many as 80% of cases are non-small cell lung cancer, and of these, at least half present as unresectable, locally advanced disease. For this subgroup of patients, the standard of care is now widely accepted to be a combined modality approach of chemotherapy and radiation therapy. What the optimal combination of these two is remains an area of continuing refinement. However, while the search for the best chemotherapeutic agents and the most effective radiation regimen continues, there is general agreement regarding the sequencing of the two components, with concurrent administration of chemotherapy and radiation being the preferred approach.
Six major randomized trials currently exist addressing various components of the sequential vs. concurrent issue. Of these, the Japanese group and RTOG have directly compared sequential vs. concurrent regimens and demonstrated a gain in median survival of about 3 months, from 11 months with sequential to 14 months with concurrent. Although this may not seem like a large absolute improvement, the 3-month increase in median survival has actually translated into a doubling of long-term survival in stage III lung cancer. While acute toxicity data indicated significantly higher grade 3+ esophagitis in the concurrent arms of the Japanese and RTOG 9410 trials, as compared to sequential, long-term toxicities actually do not appear to differ. In light of this, the concurrent arm does indeed emerge the winner, giving improvement in survival without increasing long-term morbidity.
Future directions to improve on these results should incorporate the novel biologic agents, as well as newer chemotherapeutic agents such as docetaxel. Finally, continuing refinements in radiation therapy planning and delivery will hopefully contribute to better survival in locally advanced lung cancer.