Dose Optimization in Oncology Drug Development: The Emerging Role of Pharmacogenomics, Pharmacokinetics, and Pharmacodynamics.

ABSTRACT: Drugs' safety and effectiveness are evaluated in randomized, dose-ranging trials in most therapeutic areas. However, this is only sometimes feasible in oncology, and dose-ranging studies are mainly limited to Phase 1 clinical trials. Moreover, although new treatment modalities (e.g., small molecule targeted therapies, biologics, and antibody-drug conjugates) present different characteristics compared to cytotoxic agents (e.g., target saturation limits, wider therapeutic index, fewer off-target side effects), in most cases, the design of Phase 1 studies and the dose selection is still based on the Maximum Tolerated Dose (MTD) approach used for the development of cytotoxic agents. Therefore, the dose was not optimized in some cases and was modified post-marketing (e.g., ceritinib, dasatinib,

SUBMITTER: Papachristos A 

PROVIDER: S-EPMC10296931 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature