assumed that the appropriate representation of dose level has been de-termined prior to specification of the dose-toxicity model.1.3.Choice of Starting DoseIn cancer therapy, the phase I trial often represents the first time aparticular treatment regimen is being administered to humans. Due toconsequent safety considerations, the starting dose in a cancer phase Itrial is traditionally a low dose at which no significant toxicity isanticipated. For example, the initial dose is frequently selected on thebasis of preclinical investigation to be one-tenth of the murine equivalentLD10(the dose that produces 10% mortality in mice) or one-third thetoxic dose low (first toxic dose) in dogs (Geller, 1984; Penta et al., 1992).Conversely, several authors (e.g., O’Quigley et al., 1990) suggest that thestarting dose should correspond to the experimenter’s best prior estimateof the MTD, which may not be a conservative initial level. This may beappropriate since starting the trial at a dose level significantly below the
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