Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial
P Bougnoux1,2, N Hajjaji1,2, M N Ferrasson1,2, B Giraudeau3, C Couet1,4 and O Le Floch1,2
1. INSERM U921 ‘Nutrition, Croissance et Cancer’, Tours, France
2. Henry S. Kaplan Cancer Center, University Hospital Bretonneau, University François Rabelais, Tours, France
3. INSERM CIC 202, University Hospital Bretonneau, University François Rabelais, Tours, France
4. Nutrition Department, University Hospital Bretonneau, Tours, France
Correspondence: Professor P Bougnoux, INSERM U921, H.S. Kaplan Cancer Center – CHU Bretonneau, 2 bis Boulevard Tonnellé, TOURS 37 044, France. E-mail: firstname.lastname@example.org
Received 14 July 2009; Revised 16 October 2009; Accepted 19 October 2009; Published online 17 November 2009.
Background: Breast cancer becomes lethal when visceral metastases develop. At this stage, anti-cancer treatments aim at relieving symptoms and delaying death without resulting in additional toxicity. On the basis of their differential anti-oxidant defence level, tumour cells can be made more sensitive to chemotherapy than non-tumour cells when membrane lipids are enriched with docosahexaenoic acid (DHA), a peroxidisable and oxidative-stress-inducing lipid of marine origin.
Methods: This open-label single-arm phase II study evaluated the safety and efficacy (response rate), as primary end points, of the addition of 1.8 g DHA daily to an anthracycline-based chemotherapy (FEC) regimen in breast cancer patients (n=25) with rapidly progressing visceral metastases. The secondary end points were time to progression (TTP) and overall survival (OS).
Results: The objective response rate was 44%. With a mean follow-up time of 31 months (range 2–96 months), the median TTP was 6 months. Median OS was 22 months and reached 34 months in the sub-population of patients (n=12) with the highest plasma DHA incorporation. The most common grade 3 or 4 toxicity was neutropaenia (80%).
Conclusion: DHA during chemotherapy was devoid of adverse side effects and can improve the outcome of chemotherapy when highly incorporated. DHA has a potential to specifically chemosensitise tumours.
Keywords: DHA supplementation, breast cancer chemotherapy, tumour sensitisation, survival, clinical trial