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

Phase 1 oncology trials are mainly designed to establish the recommended dose of an investigational medicinal product for further assessment. Typically, consecutive cohorts of patients receive increasing doses until a predefined dose-limiting toxicity is noted. The predefined percentage cutoff of patients who have toxic effects at a specific dose level would in turn determine the maximum tolerated dose. The role of a meal on gastrointestinal toxicity and maximum tolerated doseMolecularly targeted drugs have different toxicity profiles and dose responses compared with conventional cytotoxic drugs. These differences challenge the traditional definition of dose-limiting toxicity established for cytotoxic drugs and the assessment of maximum tolerated dose and recommended dose in phase 2 studies.1,2 In their Comment, Han Hsi Wong and Sarah Halford3 provide an excellent and timely discussion on dose-limiting toxicity and maximum tolerated dose for phase 1 oncology trials of molecularly targeted agents. Full-Text PDF