A new function for drug combination dose finding trials.

Combination drugs play an essential role in treating cancers. The challenging part of the combination drugs are to specify the dose-toxicity ordering, which means the sequences of dose escalation and de-escalation in process of dose findings should be pre-determined. In the paper, we extend a novel function of the continual reassessment method based on the combination of the normal distribution for drug-combination dose-finding trials and systematically evaluate its performance using a template of four performance measures EARS (Efficiency, Accuracy, Reliability, Selection). Dose escalation and deescalation rules are based on the nearest neighborhood continual reassessment method for a combination drug, and we specify all possible dose-toxicity orderings in the trial. Simulation demonstrates that the new design is efficient, accurate and reasonably reliable.