Two Drugs Versus One Drug in Non–Small-Cell Lung Cancer: Are We Asking the Right Questions?

The treatment of oncologic diseases has evolved after decades of exhaustive, time-consuming, expensive, and frequently inefficient trial and error. With a limited arsenal of therapeutics, basic questions regarding the dose, schedule, and optimal combination of therapeutics dominated the research landscape for many years. Throughout the 20th century, cancer-drug discovery had largely occurred through serendipitous events; chief among these events included the observations of the effects of mustard gas on soldiers during World War I, the effects of folate and plant products on the growth of leukemic cells, and the death of bacterial cells in a water basin exposed to electrodes made of platinum. These observations were followed years later by a greater understanding of the mechanisms that caused this cancer-kill effect. Several key principles of treatment emerged from the successful treatment of acute leukemia that would be tested over and over again for the next four decades, namely, the most effective treatment for cancer would come from the combination of drugs that had a singleagent activity, differing mechanisms of action, nonoverlapping toxic