{"entity":{"id":"dose-limiting-toxicity","kind":"term","name":"Dose-limiting toxicity (DLT)","aka":["DLT","DLTs","dose-limiting","dose limiting toxicity","dose-limiting toxicities","DLT period","DLT window","no DLTs","DLT rate"],"tldr":"A side effect in an early trial severe enough (usually grade 3 or worse, or forcing a long treatment pause) that the dose cannot safely go higher. Counting DLTs at each dose level is how phase 1 trials find the maximum tolerated dose.","summary":"Protocols define DLTs in advance (typically grade ≥3 non-haematological toxicity, prolonged grade 4 neutropenia, febrile neutropenia, or inability to deliver a set fraction of planned dose) and observe them over a fixed window, usually the first cycle. If a pre-set proportion of patients at a dose (2 of 6 in a 3+3 design) have DLTs, that dose exceeds tolerance. The one-cycle window misses cumulative and late toxicities (neuropathy, ILD, ocular effects), a recognised limitation for continuously dosed targeted drugs and ADCs that Project Optimus and time-to-event designs aim to correct.","asOf":"2026-09-09","links":[{"label":"NCI Dictionary of Cancer Terms: dose-limiting","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/dose-limiting"}],"tags":[],"related":["mtd","rp2d","dose-escalation-design","ctcae-grading"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-22"},"route":"/terms/dose-limiting-toxicity/","neighbours":{"term":[{"id":"ctcae-grading","kind":"term","name":"CTCAE toxicity grading (grade 3-4 adverse events)","route":"/terms/ctcae-grading/"},{"id":"dose-escalation-design","kind":"term","name":"Dose-escalation designs (3+3, BOIN, dose-expansion)","route":"/terms/dose-escalation-design/"},{"id":"febrile-neutropenia","kind":"term","name":"Febrile neutropenia","route":"/terms/febrile-neutropenia/"},{"id":"mtd","kind":"term","name":"Maximum tolerated dose (MTD)","route":"/terms/mtd/"},{"id":"project-optimus","kind":"term","name":"Project Optimus","route":"/terms/project-optimus/"},{"id":"rp2d","kind":"term","name":"Recommended phase 2 dose (RP2D)","route":"/terms/rp2d/"},{"id":"therapeutic-index","kind":"term","name":"Therapeutic index (therapeutic window)","route":"/terms/therapeutic-index/"}],"section":[{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"}]}}