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The Pharmacogenomics of Paclitaxel in Patients With Ovarian Cancer: Predictors of Toxicity and Response

18 Years
Open (Enrolling)
Ovarian Neoplasms, Fallopian Tube Neoplasms

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Trial Information

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.

Inclusion Criteria:

- Clinical diagnose and histology of invasive epithelial ovarian/tuba or peritoneal

- FIGO stage IIb-IV any grade or FIGO Ia-IIa only grade 3 or clear cell carcinoma (any
stage and grade)

- Natural candidate for paclitaxel 175mg/m2 + Carboplatin (AUC=5-6)

- Baseline CA125≥70 AND/OR evaluable disease after RECIST (incl ultrasound)

- 18 years or older

- Caucasian (ie.parents and grandparents are Caucasian)

- Performance status 2 or lower (after WHO/ECOG)

Exclusion Criteria:

- Prior malignant disease apart from cervical carcinoma in situ and basal cell
carcinoma of the skin

- Prior chemo / radiotherapy

- Ongoing or imminent other chemotherapies

- Pregnant or lactating

- Fertile woman of childbearing potential not willing to use adequate contraception

- Neurological symptoms (any kind) worse than CTCAE grade 1

- Active infection or other serious disease that could impair on treatment and/or

Type of Study:


Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Principal Investigator

Kim Brøsen, phd

Investigator Role:

Study Director

Investigator Affiliation:

University of Southern Denmark


Denmark: Danish Dataprotection Agency

Study ID:




Start Date:

September 2006

Completion Date:

March 2013

Related Keywords:

  • Ovarian Neoplasms
  • Fallopian Tube Neoplasms
  • CYP2C8
  • MDR1
  • Pharmacogenetics
  • Paclitaxel
  • Neoplasms
  • Fallopian Tube Neoplasms
  • Ovarian Neoplasms