A Phase 2 Study to Assess the Immunomodulatory Capacity of a Lecithin-based Delivery System of Curcumin in Endometrial Cancer

Abstract

Curcumin is a botanical with anti-tumor and immunomodulatory properties. We hypothesized that curcumin supplementation might influence inflammatory biomarker levels in endometrial carcinoma (EC). In this open-label, non-randomized phase 2 study (NCT02017353), seven EC patients consumed 2 g/day Curcumin Phytosome (CP) orally for 2 weeks. Blood was taken at baseline, days 1, 7, 14, and 21. The following analytes were measured: curcuminoids and metabolites, 56 inflammatory biomarkers, COX-2, frequencies of myeloid-derived suppressor cells, dendritic cells and NK cells, expression of MHC molecules on leukocytes and monocytes and activation/memory status of T cells. Patients completed quality of life (QoL) questionnaires at baseline and end of treatment. Curcumin metabolites were detectable in plasma upon CP intake. CP downregulated MHC expression levels on leukocytes (P = 0.0313), the frequency of monocytes (P = 0.0114) and ICOS expression by CD8+ T cells (P = 0.0002). However, CP upregulated CD69 levels on CD16− NK cells (P = 0.0313). No differences were observed regarding inflammatory biomarkers, frequencies of other immune cell types, T cell activation and COX-2 expression. A non-significant trend to improved QoL was observed. Overall, CP-induced immunomodulatory effects in EC were modest without significant QoL changes. Given the small population and the observed variability in inter-patient biomarker levels, more research is necessary to explore whether benefits of CP can be obtained in EC by different supplementation regimens.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02017353; www.clinicaltrialsregister.eu, identifier 2013-001737-40.

Experimental and clinical reports on anti‐inflammatory, antioxidant, and immunomodulatory effects ofCurcuma longaand curcumin, an updated and comprehensive review

“…Overall findings suggest modest immunomodulatory effects of CP in EC. 238 The effects of CUR (10-60 μM) on the T cell subtype of the immune system showed moderately enhanced IL-4 production, although IL-2 production remained unchanged. Moreover, the development of CTL was also unaffected in cancer patient.…”

Plant-Derived Nutraceuticals and Immune System Modulation: An Evidence-Based Overview

“…Furthermore, cichoric acid from echinacea promoted phagocytic activity, both in vitro and in vivo [ 53 ]. Anti-inflammatory and immune-modulatory effects has been highlighted for curcumin too, although the poor bioavailability limits its clinical application [ 54 ].…”

Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts

“…Additionally, clinical studies of phytoestrogens combined with cancer treatments are underway to observe if there is a synergistic effect to treat cancer. Here, we have reviewed 18 clinical trials [61,[227][228][229][230][231][232][233][234][235][236][237][238][239][240][241][242][243][244], conducted between 2002 to present, focused on breast cancer (seven trials) [227][228][229][230][231][232][233][234], prostate cancer (eight trials) [61,[235][236][237][238][239][240][241], endometrial cancer (two trials) [242,243], and colon cancer (two trials) [240,244], combined with two categories of phytoestrogens treatments: fruits/whole grains/seeds such as resveratrol and curcumin (eight trials) and soy isoflavones such as GEN (10 trials) (Table 3 and Supplementary Table S1).…”

“…Phytoestrogens alter cancer-related gene expression profiles in breast cancer (NCT00597532, NCT00290758, and University of North Dakota School of Medicine and Health Sciences trail), prostate cancer (NCT00546039), endometrial cancer (NCT02017353), and colon cancer (NCT00256334). More interestingly, some of the trials have shown that phytoestrogens are altering the cancer-related gene expression profiles [227,233,238,243,244]. Under the concept of personalized medicine, gene expression analyses could be an alternative and cost-effective way to predict the effectiveness of phytoestrogens in cancer prevention and treatments.…”