The addition of intravenous omega-3 fatty acids to anti-tumor medications for pancreatic cancer may improve quality of life (QOL) and clinical response, according to researchers from the University Hospitals of Leicester, UK. The authors report that the first clinical trial of intravenous (IV) ω-3FAs as a therapeutic agent in any cancer setting was very encouraging. The results warrant further study in large-scale randomized trials.
The aim of the study was to assess if IV ω-3 lipid emulsion could augment the antitumor activity of gemcitabine in patients with advanced pancreatic cancer (APC). They also aimed to assess improvement in QOL and tolerability of chemotherapy regimens.
Patients were given 1,000 mg of gemcitabine weekly followed by up to 100 g of omega-3 rich lipid emulsion for three weeks followed by a rest week. This was continued for up to six cycles, progression, unacceptable toxicity, patient request, or death. The study found evidence of activity in response and disease stabilization rates, reduction in liver metastasis volume, and improved quality of life scores in this group of patients.
ABSTRACT
Marine-derived ω-3 fatty acids (ω-3FAs) have proven antitumor activity in vivo and in vitro and improve quality of life (QOL) in clinical cancer studies. These changes may be mediated by reduction in circulating proangiogenic and proinflammatory factors. In this first study of intravenous ω-3FAs as a therapy in cancer patients, we aimed to assess if it could augment the antitumor activity of gemcitabine in patients with advanced pancreatic cancer and improve QOL. Materials and Methods: Patients were administered gemcitabine 1000 mg/m3 weekly followed by up to 100 g (200 mg/mL) of ω-3 rich lipid emulsion for 3 weeks followed by a rest week. This was continued for up to 6 cycles, progression, unacceptable toxicity, patient request, or death.
The primary outcome measure was objective response rate, with secondary outcome measures of overall and progression free survival, QOL scores, and adverse events. Results: Fifty patients were recruited. Response rate was 14.3% and disease control rate was 85.7%. Overall and progression free survival were 5.9 and 4.8 months, respectively. Increase in global health of > 10% over baseline was seen in 47.2% of patients. More than 50% of patients had > 10% increase in QOL scores in generic symptom scores and both disease-specific domains. Grade 3/4 adverse events were thrombocytopenia (8%), neutropenia (12%), nausea or vomiting (4%), and chills (6%). Conclusion: Intravenous ω-3FAs in combination with gemcitabine shows evidence of improved activity and benefit to QOL in patients with advanced pancreas cancer and is worthy of investigation in a randomized phase III trial.
Conclusion
QOL and pain scores appear to be improved by the combination of gemcitabine and IV ω-3 rich lipid infusion over baseline. Perhaps the most striking results are those of the proportion of patients with a 10% or better improvement in global health from baseline. As previously stated, 10% improvement in QOL indices is now recognized as clinically significant, and it is certain that global health is probably the most useful tool of the domains measured.
The only large phase III study assessing the improvement in QOL with single-agent gemcitabine had suggested that 29% of patients experienced a 10% or greater improvement in global health. The data from the present study of gemcitabine and IV ω-3 rich lipid infusion suggest that 47.2% of patients experience this improvement, which is certainly encouraging.
Rates of clinical benefit and improvement in several other domains of QOL were also higher than have been seen with existing regimens, but further evaluation in phase III randomized controlled trials is required to fully assess this. Improvements in QOL alone even without tumor response or survival advantages would have a great effect on the management of patients with APC but could also be of utility in the treatment of other tumor types.
This study shows that the combination of IV ω-3 rich lipid emulsion and gemcitabine is safe and feasible and may have clinical activity in patients with APC. The researchers suggest a phase III randomized controlled trial to assess the independent contribution of ω-3 lipids to this effect.
