Safety, pharmacokinetics and pharmacodynamics of targeted anti-cancer drugs

摘要: With the emergence of novel, rationally designed anti-cancer drugs there is also a need for novel endpoints when evaluating these in clinical trials. The combined PET/CT scanner can be very useful tool process drug development several ways, which described first chapter this thesis. used patient selection, measuring early response to treatment, and determining pharmacokinetics pharmacodynamics drugs. The next describes class aurora kinase inhibitors. First, experience with inhibitors A, B, or both reviewed. Following review article, phase I study one agents, AZD1152, described. In subsequent chapters thesis, trials are variety drugs, various mechanisms action. These agents include: AZD5438, an inhibitor cyclin dependent kinases; olaparib (AZD2281), PARP inhibitor; E7080, angiogenesis PF00299804, HER-1, HER-2, HER-4 receptor tyrosine kinases. Also, studies combining targeted conventional chemotherapy main goal all thesis was determine maximum tolerable dose (MTD), dose-limiting toxicities (DLTs), investigational However, increasingly important pharmacodynamic endpoints, give indications activity Several have successfully implemented assays, trial as best example. study, target inhibition (reduced enzyme poly(ADP-ribose)polymerase) demonstrated white blood cells well tumor from patients following treatment olaparib. One conclusions results that no at MTD since maximal already obtained lower doses Several showed promising activity. Olaparib, instance, appeared effective BRCA deficient breast ovarian cancer (over half tumors derived benefit olaparib). led reductions volume melanoma who entered study. Finally, partial responses were observed non-small cell lung pan-HER PF00299804. In conclusion, agents. compounds now under evaluation II III studies. Future should focus more on future included based their characteristics. might helpful purposes.