Sequential chemotherapy: rationale and clinical trial design in advanced non-small-cell carcinoma

Recent developments in the chemotherapy of advanced and metastatic non small-cell lung cancer have led to significant, albeit modest, improvements in survival and quality of life. The plethora of new agents with activity in this disease has led to questions as to how these drugs can best be added to existing regimens. Traditionally, the paradigm of combination chemotherapy has dominated this approach with new agents added to older regimens. Unfortunately, this will frequently lead to additive toxicity and necessitate reduction in the doses of individual components of the combination. The planned sequential administration of new chemotherapy agents circumvents this problem. Additionally, considerable theoretical, biological, and clinical evidence supports this approach. This paper reviews the rationale for this strategy and discusses initial data from a pilot trial of this approach.