Introduction
toxicity, cancer
CANCER, DISEASES
Drug combination therapy provides an important method for the treatment of difficult diseases such as cancer. The purpose of drug combination therapy is to induce synergistic therapeutic effects, increase the combined dose intensity, and achieve better therapeutic effects without cross-toxicity. The purpose of a drug combination dose escalation trial is to identify the maximum tolerated dose combination (MTDC) based on a prespecified target toxicity rate. In a single-drug dose escalation trial, toxicity is typically assumed to increase with an increasing dose. However, the order of toxicity between dose combinations in two-drug combination trials is only partially known. If the dose of one drug in the combination increases while that of the other drug decreases, it is unknown whether the toxicity increases or decreases (Fig. Partial toxicity order as shown. The probability of toxicity is greater for the A1B2 combination than for A1B1. In drug combination trials, the order of toxicity for all dose combinations is not entirely clear (e.g., between A2B1 and A1B2)Example of equivalent contour lines based on DLT probability for multiple dose combinationsThe rest of this paper is organized as follows. In Section 2, the BOIN design, the BOINcomb design, and the improved BOINcomb design, denoted as asBOINcomb design, are presented. In Section 3, a simulation study is used to evaluate our proposed design. The results of the simulation study are also analyzed. Section 4 uses a trial example to illustrate our proposed design. Section 5 provides some brief discussions. Finally, a summary is presented in Section 6.