Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011 Feb 15. doi: 10.1002/cncr.25933. [Epub ahead of print.]
Forty-six patients with a diagnosis of non-small cell lung cancer (NSCLC) completed the study. All patients received a standard first line chemotherapy regime (carboplatin with either vinerelbine or gemcitabine). The standard of care (SOC) arm (n=31) received only the chemotherapeutic agents; the fish oil (FO) arm (n=15) consumed 2.5 grams EPA/DHA per day in addition to their chemotherapy. Study duration was one year.
Assessments were made using imaging and clinical examination. Measures included response rate (complete response + partial response) and clinical benefit (complete response + partial response + stable disease divided by the number of patients).
Overall favorable response rate in the FO group was more than double that of the SOC group (60% vs. 25.8%, P= 0.008). Clinical benefit was also higher in the FO group vs. SOC group (80% vs. 41.8%, P= 0.2). There was a trend toward improved survival at the 1-year point in the FO group as well (60% vs. 38.7%, P= 0.15). Lastly, dose limiting toxicities did not differ between the two groups (P=0.46).
Previous studies in vitro and in vivo have shown omega-3 fatty acids may increase the cytotoxicity of chemotherapy agents.1,2 While such preliminary evidence points to potentiation of chemotherapy, there is little clinical trial data to date to substantiate these claims. The current abstract strengthens the body of evidence that suggests EPA/DHA may sensitize cancer cells to the cytotoxic effects of chemotherapeutics. It is also the first to demonstrate this effect in NSCLC patients specifically.
While this study used a platinum-based chemotherapeutic and either gemcitabine or navelbine, the effect may not be dependent on the specific chemotherapy agents used. There was a phase II study of metastatic breast cancer patients receiving anthracycline based chemotherapy and 1.8 grams/day of DHA from an algal source. Dosing began 7–10 days before the start of chemotherapy and continued throughout. In addition to overall survival, this study assessed DHA incorporation into phospholipids and found that incorporation varied greatly between individuals. Only those considered “high incorporators” had an increase in overall survival.3 One hypothesis of how omega-3 fatty acids may potentiate cytotoxic agents is through increasing the oxidative potential of the phospholipid bilayer. Increased overall survival only in those womenwho were “high incorporators” of DHA supports this hypothesis.
This bolsters the case for inclusion of omega-3 fatty acids in all patients with NSCLC undergoing chemotherapy.
Earlier studies in rodents suggested DHA may convert chemo-resistive mammary tumors to chemosensitive and radiosensitive tumors.4 The chemosensitization was nullified when alpha-tocopherol was given concomitantly, again supporting the role of lipid peroxidation as the mechanism of action. Other mechanisms of chemosensitization that have been proposed include influencing signaling proteins such as Ras, Akt, and Her2neu, altering expression or function of apoptotic proteins, affecting survival factors such as NF-KappaB, or increasing drug uptake or activation.5
It should be noted that the best-evidenced use of fish oil supplementation in integrative cancer care is not for chemo-sensitization but as an anti-cachectic agent.6 In regard to lung cancer specifically, one study showed that patients with sarcopenia (muscle wasting) have significantly less plasma EPA, DHA, and total fatty acids after 2.5 months of chemotherapy.7 Another study of patients with lung cancer given fish oil in supplement form showed improved appetite, less fatigue, and lowered C-reactive protein.8 In a separate publication, the authors of the current abstract showed that muscle mass was better preserved in NSCLC patients who consumed 2.2 grams of EPA//DHA during treatment versus those just receiving standard of care.9 While preservation of muscle mass is enough reason to recommend supplementation with EPA/DHA in NSCLC patients, the current study suggests response rates and overall survival may also benefit. Certainly, this bolsters the case for inclusion of omega-3 fatty acids in all patients with NSCLC undergoing chemotherapy.
This is a small study of only 46 participants. Nonetheless, it did reach statistical significance. There was no placebo used in the group that did not take fish oil. A placebo control would strengthen the findings considerably, as it is possible that those patients healthy enough to swallow addition pills would be expected to have longer survival as well.
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1. Hardman WE, Avula CP, Fernandes G, Cameron IL. Three percent dietary fish oil concentrate increased efficacy of doxorubicin against MDA-MB 231 breast cancer xenografts. Clin Cancer Res. 2001;7:2041-2049
2. Germain E, Lavandier F, Chajès V, et al. Dietary n-3 polyunsaturated fatty acids and oxidants increase rat mammary tumor sensitivity to epirubicin without change in cardiac toxicity Lipids. 1999;34:S203.
3. Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le Floch O. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer. 2009;101:1978-1985.
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7. Murphy RA, Mourtzakis M, Chu QS, Reiman T, Mazurak VC. Skeletal muscle depletion is associated with reduced plasma (n-3) fatty acids in non-small cell lung cancer patients. J Nutr. 2010;140:1602-1606.
8. Cerchietti LC, Navigante AH, Castro MA. Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Nutr Cancer. 2007;59:14-20.
9. Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer. 2011;117:1775-1782.