Project details


Phase Ib study of metformin in combination with carboplatin/paclitaxel chemotherapy in patients with advanced ovarian cancer: pharmacokinetics.

chemotherapy pharmacokinetics metformin

dr. M. Jalving
K.E. Broekman
Prof dr A.K.L. Reyners

Type of project:
Stage Wetenschap / Research project

Nature of the research:
Pharmacokinetic analysis of carboplatin/paclitaxel chemotherapy with and without metformin in advanced ovarian cancer. This research project is especially suitable for students with experience in pharmacology.

Fields of study:
pharmacology oncology

Background / introduction
Molecularly targeted agents which inhibit the mTOR pathway and/or
circumvent p53 in the induction of apoptosis are exciting potential targets in ovarian cancer. Metformin is a biguanide, widely used in the treatment of type 2 diabetes mellitus,
that has shown anti-cancer activity in preclinical studies. The main mechanism of metformin’s effect is mTOR pathway inhibition and, in addition, it has been shown to
circumvent p53-induced apoptosis making it an exciting, potentially effective drug in ovarian cancer.
Research question / problem definition
The primary objective of this research project is to document the influence of metformin on the pharmacokinetics of carboplatin/paclitaxel chemotherapy.
This research project is part of a phase Ib, single-centre, dose-escalation trial of metformin added to carboplatin/paclitaxel chemotherapy. 12 patients are included for this part of the study. Of all patients blood samples were collected at different time points during chemotherapy cycle 1 (without metformin) and chemotherapy cycle 2 (with metformin). Drug levels of metformin, carboplatin and paclitaxel will be measured in cooperation with the department of pharmacology and the pharmacokinetics of the three drugs will be evaluated.
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