Off-label, but on target: the evidence needed to implement alternative dosing regimens of anticancer drugs.

Over the past decades, dose selection of anticancer drugs has been dictated by the maximum tolerated dose (MTD), based on tolerability rather than efficacy.1 Tolerability-driven dose selection is an efficient strategy to select a relatively safe dose over a short timeframe in a limited number of patients for development of the drug in subsequent further clinical trials focusing on efficacy.2 This method of dose selection disregards exposure–response relationships, interpatient variability in pharmacokinetic drug exposure, long-term safety, and patient convenience.