A new, single-arm, phase 2 trial conducted at Leicester University Hospital in the UK has shown that the administration of intravenous marine omega-3 fatty acid emulsions to patients with advanced pancreatic cancer being treated with the chemotherapy drug gemcitabine improves antitumor efficacy and quality of life.
Metabolic derivatives of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) produce anti-inflammatory compounds that regulate pro-inflammatory and pro-angiogenic growth factors. Specifically, EPA and DHA are capable of downregulating the production of the pro-angiogenic cytokines that cause cachexia (severe muscle wasting) in patients with advanced cancer. Any relief from the progression of cachexia will significantly improve the quality of life of the patient.
Pancreatic cancer is a particularly distressing form of the disease. It proceeds rapidly and the survival duration is short, during which time there is a rapid deterioration in quality of life (QOL). The palliative treatment in recent years has been a monotherapy involving the intravenous infusion of the cytotoxic, antimetabolite drug gemcitabine. Such cytotoxic drugs not only kill cancer cells but can kill some healthy cells, too. One consequence of this is a progressive muscle wasting condition known as cachexia. In addition, patients suffer from nausea, chills, anemia, and infections, resulting in a rapid overall reduction in QOL.
DHA is known to regulate controlled cell death (apoptosis). One specific derivative, 17-HpDHA, is known to be cytotoxic to cancer cells (3). The debilitating cachexia found in almost all progressive cancer patients can be managed by downregulating the production of pro-angiogenic cytokines. Metabolites of DHA and EPA attenuate pro-angiogenic cytokine production (2).
In the current phase 2 trial, 36 patients were assessed for changes in QOL scores after receiving an intravenous infusion of an omega-3 emulsion (Lipidem), providing around 4.3–8.6 g EPA and DHA, in addition to their treatment with the chemotoxic drug gemcitabine (1) (note that the use of IV omega 3 emulsion overcomes the problems of consuming such high levels by the oral route). The result was an improvement in terms of stabilizing the disease and a reduction in liver metastasis, although there was no improvement in overall survival rates. Most importantly, overall QOL scores increased by 10%, which is regarded as clinically significant. This was the first trial of its kind and the authors have suggested that the results justify a full phase 3 randomized trial to confirm the positive effects.
