The Pharmacogenomics of Paclitaxel in Patients With Ovarian Cancer: Predictors of Toxicity and Response
Paclitaxel is an antineoplastic drug used in the treatment of ovarian cancer. The effect and
toxicity is unpredictable in the individual patient. Paclitaxel is removed (eliminated) from
the organism by oxidation. CYP2C8 is the enzyme mainly responsible. P-glycoprotein (Pgp) is
an efflux transport protein natural to the human organism. Pgp is responsible for excretion
of drugs via the bile and the kidneys and is thought to play a role in chemotherapy
resistance. Paclitaxel is substrate for Pgp. Single nucleotide polymorphisms are possible
causes for variation in both CYP2C8 and Pgp expression/function. We will study a possible
role of these genetic variations as predictors of paclitaxel toxicity and effect and the
possible implications for individual dosing in the future.
We want to determine the metabolic capacity of approximately 100 ovarian cancer patients and
comparing this with genotypes, acute toxicity(eg. bone marrow suppression and neuropathy)
and response to treatment(ie. CA125 response, progression free survival and overall
survival). The metabolic capacity is estimated using a "sparse sampling" approach applying
advanced computerized pharmacokinetic/dynamic modelling as opposed to traditional "frequent
sampling" pharmacokinetic studies which burden the individual patient more.
Patients are recruited in collaboration with Oncological departments throughout Scandinavia.
Observational Model: Cohort, Time Perspective: Prospective
Kim Brøsen, phd
University of Southern Denmark
Denmark: Danish Dataprotection Agency