Curcumin in endometrial cancer
Effect of curcumin addition to standard treatment on tumour-induced inflammation in endometrial carcinoma.
- Gynaecological cancer
Why this trial?
Uterine tumours can be subdivided in endometrial carcinoma and uterine sarcoma. Uterine carcinomas occur in 1 in 70 Belgian women. Endometrial carcinoma displays several features of inflammation, including cytokine secretion and leukocyte infiltration in tumours. It is hypothesized that hormonal alterations and genetic changes in tumour cells create a pro-inflammatory environment that facilitates cancer progression. Several cytokines and chemokines have been associated with endometrial carcinoma and the tumour cells also have been shown to express molecules to escape anti-tumour immunity.
Therapeutic options (surgery, chemotherapy, radiotherapy) are limited in recurrent endometrial carcinomas. The prognosis in these patients remains poor. The five-year survival rate in advanced stages is less than 10%. As a result, the search for new therapeutic options is mandatory.
Why this drug?
Curcumin, or diferuloylmethane, is the major constituent and the active component in the spice turmeric and is available as food supplement, not as a drug. Curcumin preparations have been used in various clinical trials in cancer or other diseases in doses up to 8 g daily without major side effects and is generally recognised as safe by the FDA.
Curcumin has shown direct effects on tumour cells as well as anti-inflammatory effects. Activity against all phases of cancer development – initiation, promotion, proliferation and metastasis – has been demonstrated in preclinical work. Curcumin has been explored by others in clinical trials both as a preventive and therapeutic agent with promising results.
It is a pleiotropic molecule capable of interacting with numerous molecules involved in inflammation. The anti-inflammatory properties of curcumin include: (1) downregulation of several inflammatory enzymes, (2) inhibition of inflammatory cytokine secretion, and (3) inhibition of inflammation-mediated PD-L1 expression.
Both in vitro cell culture experiments as well as in vivo experiments in mouse models have revealed that curcumin can sensitise tumour cells to other treatments, such as the cytocidal effects of radiation and different chemotherapeutic agents. This chemotherapy sensitisation phenomenon has been observed in several cancer types.
The exploration of curcumin as a therapeutic anti-cancer agent has been severely hampered by its poor systemic availability. Consequently, efforts have been dedicated to the development of alternative formulations of curcumin to enhance its bio-availability. Meriva is an optimized formulation.
This was a monocentric, prospective phase II trial to determine the capacity of curcumin to reduce inflammatory mediators and immunomodulatory cell types in endometrial carcinoma. The food supplement containing Meriva, CurcuPhyt, was administered orally daily for 2 weeks before initiating standard treatment in patients with a recurrence of endometrial carcinoma and with no life-threatening metastases. The blood level of several inflammatory mediators, immunomodulatory cell types and curcuminoids: demethoxycurcumin and curcumin and its conjugates (glucuronide and sulfate) were measured at regular intervals during treatment to determine the capacity of curcumin to reduce inflammation and its bioavailability. The toxicity of curcumin and the quality of life of the patients were also evaluated.
Due to slow recruitment, the trial was closed after inclusion of 7 patients. Inflammatory markers and immune cells from both blood and tumour biopsies were analysed, as well as the availability of curcuminoids in the plasma and urine of the patients. A report is expected to be published in the Q1-2 of 2018.
- PhD. Sandra Tuyaerts, Oncology Dept., Gynecologic Oncology Division, University Hospital Leuven, Leuven, Belgium
- University Hospital Leuven, Leuven, Belgium
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