Phase I cancer trials: limitations and implications.

The goal of Phase I clinical trials is to establish a maximum tolerated dose (MTD) and a tolerable dose range for future efficacy testing. Various issues include schedule of drug delivery, starting dose, number of patients to be tested, pitfalls in the selection of MTD, risk:benefit ethical issues, and the problems introduced by patient heterogeneity. Statistical evaluation of various Phase I strategies illustrate the limitations of various approaches in terms of patient expectations regarding efficacy and the scientific goals of such trials. Patients should be given the opportunity to receive the drug at more than one single dose level.