Theory and practice of clinical pharmacodynamics in oncology drug development.
The clinical development of molecularly targeted cancer therapies is enhanced by proof of mechanism of action as well as proof of concept, which relate molecular pharmacodynamics to efficacy via changes in cancer cell biology and physiology resulting from drug action on its intended target. Here, we present an introduction to the field of clinical pharmacodynamics, its medical and laboratory aspects, and its practical incorporation into clinical trials. We also describe key success factors that are useful for judging the quality of clinical pharmacodynamic studies, including biopsy quality and suitability, specimen handling, assay fitness-for-purpose, and reagent quality control. This introduction provides not only context for the following articles in this issue, but also an appreciation of the role of well-conducted clinical pharmacodynamic studies in oncology drug development.
Clinical Pharmacodynamics Program, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD. Electronic address: parchmentr@mail.nih.gov.
Ralph E
RE
Parchment
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD.
James H
JH
Doroshow
D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001706:Biopsy; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000379:methods*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068877:Imatinib Mesylate
Assay fitness-for-purpose; Biopsy sample quality; Biopsy surrogate tissues; Reagent quality control