The basic concept is the dose of a chemotherapeutic agent above which there is excessive risk from toxicity.
Factors impacting the definition (Le Tourneau et al):
(1) duration of the toxicity
(1a) the period over which toxicity is assessed
(1b) minimum duration of toxicity
(1c) reversibility of toxicity within a certain period of time
(2) severity of the toxicity
(2a) absolute severity in the NCI CTC adverse event classification
(2b) severity relative to baseline
(3) impact of the toxicity
(3a) need to delay treatment or to reduce the dose
CTC Grade III or IV toxicities are usually considered DLT unless the toxicity can be managed or the toxicity is considered acceptable for the benefit. For example, severe transient thrombocytopenia that does not require transfusion may not be considered a DLT.
A CTC Grade II may be considered to be a DLT if it is disabling.
The DLT is often biased towards acute severity versus delayed effects. For example, the total dose of adriamycin may be limited due to concerns of cardiotoxicity.
