Short summary

Paclitaxel is an effective chemotherapeutic drug used to treat several cancers such as breast- and ovarian cancers. While effective, paclitaxel causes substantial dose-limiting peripheral neuropathy among patients treated with the drug. Atorvastatin is a cholesterol-lowering drug that is used by more than 300,000 patients on a yearly basis in Denmark alone. In this project, we will determine if concomitant administration of paclitaxel and atorvastatin leads to higher risk of peripheral neuropathy.

Rationale

Paclitaxel is an effective chemotherapeutic drug used to treat several cancers such as breast- and ovarian cancers. While effective, paclitaxel causes substantial dose-limiting peripheral neuropathy among patients treated with the drug. These painful symptoms occur due to damage to cell in the peripheral nervous system. Paclitaxel is a well-known substrate of the efflux transporter P-glycoprotein that - among other things - protects the peripheral nervous system from chemotherapeutics such as paclitaxel. 

Atorvastatin is a cholesterol-lowering drug that is used by more than 300,000 patients on a yearly basis in Denmark alone. We recently showed that atorvastain inhibits P-glycoprotein and causes accumulation of paclitaxel in neurons in the laboratory. In a Spanish cohort of patients, we showed that combining atorvastatin with paclitaxel led to a substantial increased risk of peripheral neuropathy. In order to validate this, in this project we will determine if concomitant administration of paclitaxel and atorvastatin leads to higher risk of peripheral neuropathy in a Danish cohort.

Description of the cohort

Patients with ovarian- or breat cancer treated with paclitaxel. 

Data and biological material

We will go through health records for these patients for symptoms of peripheral neuropathy.

Publications associated with the project

(Previous publication on this project - but not on these data)

Clin Pharmacol Ther. 2020 Apr 10. doi: 10.1002/cpt.1847. [Epub ahead of print]

P-glycoprotein Inhibition Exacerbates Paclitaxel Neuronal Toxicity in SH-SY5Y-derived Neurons and Cancer Patients

Stage TB, Mortensen C*, Khalaf S*, Steffensen V, Hammer HS, Xiong C, Nielsen F, Poetz O, Svenningsen ÅF, Rodriguez-Antona C, Kroetz DL.