# Dose-limiting toxicity (DLT)

Source: https://onco.cc/terms/dose-limiting-toxicity/  
OnCo record `dose-limiting-toxicity` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: DLT; DLTs; dose-limiting; dose limiting toxicity; dose-limiting toxicities; DLT period; DLT window; no DLTs; DLT rate

## Sources

- NCI Dictionary of Cancer Terms: dose-limiting: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/dose-limiting

## Connected records

- terms: [CTCAE toxicity grading (grade 3-4 adverse events)](https://onco.cc/terms/ctcae-grading/), [Dose-escalation designs (3+3, BOIN, dose-expansion)](https://onco.cc/terms/dose-escalation-design/), [Febrile neutropenia](https://onco.cc/terms/febrile-neutropenia/), [Maximum tolerated dose (MTD)](https://onco.cc/terms/mtd/), [Project Optimus](https://onco.cc/terms/project-optimus/), [Recommended phase 2 dose (RP2D)](https://onco.cc/terms/rp2d/), [Therapeutic index (therapeutic window)](https://onco.cc/terms/therapeutic-index/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)

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