Dose-limiting toxicity and maximum tolerated dose: still fit for purpose?

Abstract

Furthermore, many of these drugs are administered continuously and their toxic effects are often low grade and might be delayed in onset or be cumulative, occurring late after treatment initiation.3 Dose-limiting toxicities do not always develop and the maximum tolerated doses are often not established in trials of molecularly targeted drugs. [...]results from the recent DLT-TARGETT international survey,4 for example, are hardly surprising; most phase 1 trialists favoured a change in the definition of dose-limiting toxicity to include specific grade 2 toxic effects and a longer assessment period than normally used.