Table 1.

Glossary of terms

Term	Definition
Cohort	Group of patients treated at a dose level.
Starting dose	The dose chosen to treat the first cohort of patients in a phase I trial.
Dose increment (decrement)	The percent increase (or decrease) between dose levels.
Dose-limiting toxicity (DLT)	Toxic effects that are presumably related to the drugs that are considered unacceptable (because of their severity and/or irreversibility) and that limit further dose escalation. DLTs are defined before beginning the trial and are protocol specific. They are typically defined based on toxic effects seen in the first cycle and specified using a standardized grading criteria, for example, Common Terminology Criteria for Adverse Events.
Dose–efficacy curve	The dose–efficacy curve reflects the relationship between dose and probability of efficacy for an anticancer agent. A logistic function is commonly assumed to describe the dose–efficacy curve for cytotoxic agents and is characterized by a parameter, θ, which represents the slope of the dose–efficacy curve. Small values of θ indicate that the probability of efficacy increases very slowly with increasing dose levels, whereas large values of θ indicate a sharp increase in efficacy with increasing dose levels (seeFigure 1).
Dose–toxicity curve	The dose–toxicity curve reflects the relationship between dose and probability of toxicity for an anticancer agent. A logistic function is commonly assumed to describe the dose–toxicity curve for cytotoxic agents and is characterized by a parameter, θ, which represents the slope of the dose–toxicity curve. Small values of θ indicate that the probability of toxicity increases very slowly with increasing dose levels, whereas large values of θ indicate a sharp increase in toxicity with increasing dose levels (seeFigure 1).
Target toxicity level	The maximum probability of DLT that is considered acceptable in the trial. The target toxicity level in phase I trials is typically between 20% and 33%.
Maximum tolerated dose (MTD)	Phase I trials conducted in the United States: the highest dose level at which ≤33% of patients experience DLT.
	Phase I trials conducted in Europe and Japan: the lowest dose level at which ≥33% of patients experience DLT (a misnomer in the sense that the MTD is actually not a tolerable dose).
	Phase I trials that use model-based methods: the dose that produces the target toxicity level.
Optimal biological dose (OBD)	Dose associated with a prespecified most desirable effect on a biomarker among all doses studied (eg, inhibition of a key target in tumor or surrogate tissue or achievement of a prespecified immunologic parameter).
Recommended phase II dose	Phase I trials with a toxicity endpoint that are conducted in the United States: the MTD.
	Phase I trials with a toxicity endpoint that are conducted in Europe and Japan: one dose level below the MTD.
	Phase I trials in which the endpoint is a prespecified biological endpoint: the OBD.
Pharmacokinetics	Pharmacologic effects of the body on the drug (ie, the time course of drug absorption, distribution, metabolism, and excretion).
Pharmacodynamics	Pharmacologic effects of the drug on the body (eg, nadir neutrophil or platelet count, nonhematologic toxicity, molecular correlates, imaging endpoints).
Therapeutic index	The dosage or range of dosages of a drug that is required to produce a given level of damage to critical normal tissues (toxicity) divided by the dosage or range of dosages that yields a defined level of antitumor effect (efficacy) (seeFigure 1).