The effect of chemotherapy on coagulation in patients with locally advanced or metastasized pancreatic cancer

Cancer is associated with an increased risk of venous thromboembolism.
Especially in patients with locally advaned or metastatic pancreatic cancer the
risk is high. This risk is further increased by chemotherapeutic treatment. It
is unclear in what way chemotherapy contributes to hypercoagulability. We
hypothesize that chemotherapy-induced hypercoagulability is caused by systemic
inflammation with leukocyte activation, release of procoagulant microparticles
and subsequent acivation of the coagulation cascade.

To determine whether FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin)
chemotherapy results in an increase of inflammation-mediated procoagulant blood
factors; to determine whether CCX872-B, a CCR2-inhibitor, is able to inhibit
this increase of inflammation-mediated procoagulant blood factors

Exploratory observational study

Burden:
Patients receiving FOLFIRINOX only are asked to donate extra blood (22.4-25.1
mL) 8 times during chemotherapeutic treatment (total duration: 12 weeks).
Patients receiving FOLFIRINOX and CCX872-B are asked to donate blood (5.4 mL)
at 3 time points during 1 month of chemotherapeutic treatment. Blood is
collected from the port-a-cath system which is already punctured at those times
as part of regular patient care. Patients do not need to be punctured
additionally. Furthermore, non-invasive ultrasound imaging of both legs will be
performed in patients receiving FOLFIRINOX only two times during the study in
order to screen for asymptomatic venous thrombosis. These investigations are
painless and take about 20-30 minutes. Ultrasound imaging will be performed at
times when the patient is already visiting the hospital as part of regular
patient care. Patients do not need to visit the hospital more often.
Diseased and healthy control patients are asked to donate blood (25.1 mL by
vein puncture) only once.

Risks:
There's a chance of diagnosing an asymptomatic deep or superficial venous
thrombosis on routine ultrasound imaging of the legs. Treatment with
low-molecular-weight heparin and stockings may be started to prevent extension
of the thrombus, physical complaints and a pulmonary embolism. The
anticoagulant treatment increases the risk of bleeding. The decision whether to
treat is dependent on the site and extension of the thrombus and the estimated
risk of bleeding.