This preview shows page 1. Sign up to view the full content.
Unformatted text preview: toxicity. More precisely, the MTD is defined as the dose expected to produce some degree of medically unacceptable, dose limiting toxicity (DLT) in a specified proportion u of patients (Storer, 1989; Gatsonis and Greenhouse, 1992). Hence we have Prob f DLT j Dose MTD g u 1 where the value chosen for the target probability u would depend on the nature of the dose limiting toxicity; it would be set relatively high when the DLT is a transient, correctable, or nonfatal condition, and low when it is lethal or life threatening (OQuigley et al., 1990). Participants in cancer phase I trials are usually late stage patients for whom most or all alternative therapies have failed. For such patients, toxicity may be severe before it is considered an intolerable burden (Whitehead, 1997). Thus, in cancer phase I trials, dose limiting toxicity is often severe or potentially life threatening and the target probability of toxic response is correspondingly low, generally less than or equal to 1/3. As an example, in a phase I trialgenerally less than or equal to 1/3....
View Full Document
- Spring '11