Short summary

Chemotherapy-induced peripheral neuropathy (CIPN) is a well-known late effect cancer survivors live with as a result of systemic antineoplastic treatment. The essential n-3 poly unsaturated fatty acids (n-3 PUFA) are crucial for the development and functioning of the nervous system. Our objective is to examine if a high n-3 PUFA supplementation reduces the incidence and severity of CIPN 8 months after adjuvant oxaliplatin following surgery for high-risk colorectal cancer.

Rationale

Chemotherapy-induced peripheral neuropathy (CIPN) is one of several late effects cancer survivors live with as a result of systemic antineoplastic treatment. In patients receiving chemotherapy CIPN is seen in 30% 6 months after treatment, but the prevalence depends on the type of chemotherapy. Oxaliplatin, a third-generation platinum compound used in adjuvant treatment of colon cancer, is known to be one of the most neurotoxic chemotherapeutic agents inducing both an acute reversible neuropathy and a chronic length-dependent neuropathy.

There is no treatment for CIPN. Pain medications of different kinds have been tried without convincing effect and with a high NNT (number needed to treat) in order to achieve 50% pain relief.

The mechanisms behind CIPN are not known in detail, but there are several theories. Neuroinflammation and modulation of the immune response have been shown to be relevant mechanisms in CIPN pathogenesis and for development of neuropathic pain. Multiple studies have demonstrated increased innate neuro immune response following chemotherapy, and proinflammatory cytokine expression is generally upregulated in the nervous system following chemotherapy treatment.

The essential n-3 PUFAs, docosaexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are crucial for the development and functioning of the nervous system. DHA and EPA have been shown to inhibit inflammation in animal and cell models. The anti-inflammatory effect of n-3 PUFA is also well-known in chronic inflammatory diseases such as rheumatic arthritis and in acute settings of sepsis.

Clinical studies support significant neuroprotection from n-3 PUFA supplementation, e.g. in diabetic neuropathy. Furthermore, some studies have shown promising results of n-3 PUFA in preventing CIPN, which should be tested in a larger trial.

Description of the cohort

Patients operated for colorectal cancer and referred to the Departments of oncology and candidates for adjuvant chemotherapy containing oxaliplatin.

Data and biological material

data from patient journal: diagnosis, chemotherapy treatment regime, data from interview and examination collected during the trial period.

data from blood samples taken during the trial period.

Data from skin biopsies collected during the trial period.

data from questionnaire collected during the trial period.

Collaborating researchers and departments

Department of oncology, Aarhus University hospital,

• Christian Hviid

Department of oncology, Aalborg University hospital.

• Signe Christensen

Dpartment of oncology, Odense University hospital.

• Thea Otto Mattsson