Toxicities in RTOG combined-modality trials for inoperable non-small-cell lung cancer

Inoperable non-small-cell lung cancer has become the domain of combined-mod ality treatment based on several recent large, phase III studies. Results o f Radiation Therapy Oncology Group (RTOG) phase II studies have suggested i mprovements irt response and short-term survival, using a strategy of inten stfication of dosing and scheduling of cisplatin-based regimens and either standard or hyperfractionated radiation therapy. However, some trials also have shown higher rates of severe acute toxicity and more frequent severe l ate toxicity. There appears to be art institutional learning curve irt admi nistering these more complex, intense regimens and in effective management of the acute toxicities. As the RTOG institution accrued more cases onto th e intensified regimen studies, toxicity management improved, treatment was given with fever interruptions or dosage reductions, and survival rates imp roved. Quality-adjusted survival analysis, lit which survival time is reduc ed by the amount of time spent with severe toxicity, shows that the surviva l gains observed with some concurrent regimens may be negated by time spent with toxicity. Future attempts to optimize combined-modality therapy must take account of toxicity issues in the study design by incorporating less t oxic chemotherapy agents, normal tissue protectors, tumor-targeting sensiti zing agents, normal tissue-sparing radiation therapy techniques (eg, three- dimensional conformal) and proactive, aggressive management of toxicity.