Study: Fish oil improves the effect of chemotherapy in lung cancer patients

reference

Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Fish oil supplementation increases the effectiveness of first-line chemotherapy in patients with advanced non-small cell lung cancer.Cancer.February 15, 2011. doi: 10.1002/cncr.25933. (Epub ahead of print.)

design

46 patients diagnosed with non-small cell lung cancer (NSCLC) completed the study. All patients received standard first-line chemotherapy (carboplatin with either vinerelbine or gemcitabine). The standard-of-care (SOC) arm (n=31) received only the chemotherapy drugs; The fish oil group (FO) (n=15) consumed 2.5 grams of EPA/DHA per day in addition to chemotherapy. The duration of the study was one year.

Target parameters

Assessment was carried out 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).

Key findings

Overall, the positive response rate in the FO group was more than twice as high as in the SOC group (60% versus 25.8%).P= 0.008). The clinical benefit was also higher in the FO group than in the SOC group (80% vs. 41.8%,P= 0.2). There was also a trend toward improved survival at one year in the FO group (60% vs. 38.7%).P= 0.15). Finally, dose-limiting toxicities did not differ between the two groups (P=0.46).

Clinical implications

Previous studiesin vitroAndin vivohave shown that omega-3 fatty acids can increase the cytotoxicity of chemotherapy drugs.^1.2While such preliminary evidence suggests potentiation of chemotherapy, there is little clinical trial data to support these claims. The current summary reinforces evidence suggesting that EPA/DHA may sensitize cancer cells to the cytotoxic effects of chemotherapy drugs. It is also the first time that this effect has been demonstrated specifically in NSCLC patients.

While this study used a platinum-based chemotherapy drug and either gemcitabine or navelbine, the effect may not depend on the specific chemotherapy drugs used. There was a phase II trial in patients with metastatic breast cancer who received anthracycline-based chemotherapy and 1.8 grams per day of DHA from an algae source. Dosing began 7-10 days before starting chemotherapy and continued throughout. In addition to overall survival, this study examined DHA incorporation into phospholipids and found that incorporation varied greatly from person to person. Only those considered “high founders” experienced an increase in overall survival.³One hypothesis as to how omega-3 fatty acids may potentiate cytotoxic agents is by increasing the oxidative potential of the phospholipid bilayer. An increased overall survival rate only among women who were “heavy on DHA” supports this hypothesis.

This reinforces the case for omega-3 fatty acid intake in all patients with NSCLC undergoing chemotherapy.

Previous studies in rodents suggested that DHA could convert chemoresistant mammary tumors into chemosensitive and radiosensitive tumors.⁴Chemosensitization was abolished with concurrent administration of alpha-tocopherol, again supporting the role of lipid peroxidation as the mechanism of action. Other proposed mechanisms of chemosensitization include affecting signaling proteins such as Ras, Akt, and Her2neu, altering the 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 use of fish oil as a dietary supplement in integrative cancer treatment is best done not for chemo-sensitization, but as an anti-cachectic agent.⁶Specifically with regard to lung cancer, a study showed that patients with sarcopenia (muscle wasting) had significantly lower plasma EPA, DHA and total fatty acids after 2.5 months of chemotherapy.⁷Another study of lung cancer patients given fish oil in supplement form showed improved appetite, less fatigue, and a reduction in C-reactive protein.⁸In 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 than in those who received standard treatment alone.⁹While maintaining muscle mass is reason enough to recommend EPA/DHA supplementation in NSCLC patients, the current study suggests that response rates and overall survival may also benefit. This certainly supports the intake of omega-3 fatty acids in all patients with NSCLC undergoing chemotherapy.

Study Restrictions

This is a small study with only 46 participants. Nevertheless, it reached statistical significance. No placebo was used in the group that did not take fish oil. A placebo control would greatly strengthen the results because it is possible that patients healthy enough to swallow additional pills would also be expected to have longer survival.

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