Continuous toxicity response
toxicity, Cancer
SIDE EFFECT, CANCER
We start by characterizing some basic concepts that define a continuous toxicity response in the dose-response modeling framework. To that end, we first need to “clinically” understand two fundamental concepts: MTD and DLT, which are central to dose-finding problems in phase I trials. The mathematical definitions of MTD and DLT will be discussed in the next subsection.The aims of typical phase I oncology trials are to determine MTD, assess the safety and tolerability, and investigate the pharmacokinetics and pharmacodynamics of a new drug. The United States National Cancer Institute defines MTD as the highest dose of a drug that does not cause unacceptable side effects (Visit the website Throughout the paper, We denote an open interval Phase I trial designs for cytotoxic agents are based on the assumptions that (a) the clinical benefit of the agent increases with increasing dose, (b) the toxicity of the agent increases with increasing dose, and (c) there is a dose with acceptable toxicity that offers clinical benefit [A1. A side effect caused by the toxicity response A2. A side effect caused by the toxicity response A3. A side effect caused by the toxicity response A4. A side effect caused by the toxicity response A5. A side effect caused by the toxicity response The assumptions above are common features describing a toxicity response used in many phase I clinical trials [The following are some important implications based on the assumptions. The first assumption (A1) means that patients are expected to have no treatment effect when they are assigned a dose 