Abstract 3832: Tolerance of oral lipoid acid and hydroxycitrate combination in cancer patients: first approach of the cancer metabolism research group

Abstract

Abstract Introduction: our previous publications demonstrate that lipoïc acid (ALA) and hydroxycitrate (HCA) combination decreases the tumor growth in mice with either lung cancer, bladder cancer or melanoma. ALA is a well known treatment of the diabetic neuropathy but its interest in cancer is growing. In fact, ALA is a cofactor in mitochondrial energy metabolism and a potent regulator of the cell's redox status with effects on P13K and AMPK signaling and related transcriptional pathways. These mechanisms increase its interest in cancer and aging relative diseases. HCA (garcinia extract) a weight loss supplement, a derivated citric acid, could act by competitively inhibiting the enzyme adenosine triphosphate citrate lyase. This could also be a way to inhibit tumor cells growth as other evoked mechanisms (increase of serotonin in the brain, inhibition of pancreatic alpha amylase and intestinal alpha glucosidase leading to a reduction in carbohydrate metabolism. So, both molecules target the abnormal metabolic pathways such as seen in cancer. There combination appears in mice to be more effective than their use alone. We report here the early clinical tolerance evaluation of a daily metabolic combination in humans associated with chemotherapy. Methods and patients(p.) Italian experience: median duration of 14,5 months (4 to 20 m),4 p.: 3 F, 1 M, median age 57 years (37 - 81 y), 1 breast cancer, 1 nasopharyngeal carcinoma, a pancreatic adenocarcinoma, a glioblastoma. Doses of ALA 1,2 g/d, HCA 1,2 g/d orally. AlL but one p. had concomitant chemotherapy. French experience: Jan 08 to Nov 11, 13 p. with local relapse and/or metastatic cancer with a combination of ALA -HCA, 7 M, 6 F, median age 45 y (28 –74) 2 colon, 1 lung, 1 hepatocarcinoma, 5 sarcomas, 1 neuro-endocrine. HCA was administered orally, 3 g / d (1 g x3/d). ALA 1,8 g /D (600 m g x3/d) and from Oct 11 increased to 6 g /d for 3 last 6 p. Median duration: 3 months (15 d - 5 m, 1 pt 20m). Results: This association was well tolerated with few clinical disturbances: vomiting, nausea, 5 patients had a gastric protective treatment and 2 because of corticotherapy. The increased dose of ALA was well tolerated. No hepatic toxicity found, no weight loss, no hypoglycemia. A problem was the bad and discontinued observance for patients in relation with the cost of these medicines, the difficulty to buy them (only by online pharmacy for ALA in France).The tolerance of HCA was mild because of gastric pain but patients continue the treatment. Conclusion: ALA - HCA a combination well tolerated is a promising treatment in cancer patients. The switch to IV ALA will permit to obtain higher blood peaks and better observance. Randomized clinical trials are necessary to evaluate the efficacy on tumor progression in correlation with pharmacologic studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3832. doi:1538-7445.AM2012-3832