ABSTRACT
Treating patients with a combination of two agents is quite common in cancer therapy. Advantages of giving combinations include the potential to induce a synergistic treatment effect, target different drug susceptibilities of cancer cells, or achieve a higher overall dose intensity with non-overlapping toxicities. Trial designs for drug-combination studies involve several distinct features that are beyond the scope of methods for single-agent studies. An important feature of drug-combination trials is the outcome-probability-equivalent contour in the two-dimensional dose-Toxicity and dose-Efficacy spaces. Medically and biologically, this trial was very similar to the trial motivating the phase I–II design of M. K. Riviere, Y. Yuan, F. Dubois, and S. Zohar, since both trials addressed the problem of finding an optimal dose pair of a targeted agent combined with chemotherapy. In the design, response is assumed to be observable quickly so that each incoming patient can be randomized immediately based on the Efficacy outcomes of treated patients.
