Multicenter randomized phase II study comparing docetaxel plus curcumin versus docetaxel plus placebo in first-line treatment of metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) patients have a poor prognosis, and curcumin is known to have antineoplastic properties. On the basis of previous phase I and phase II studies, we investigated whether the association of curcumin with docetaxel could improve prognosis among mCRPC patients. METHODS: A total of 50 mCRPC patients (included from June 2014 to July 2016) treated with docetaxel in association with oral curcumin (6 g/d for 7 days every 3 weeks) versus placebo were included in this double-blind, randomized, phase II study. The primary endpoint was to evaluate the time to progression. Among the secondary endpoints, compliance, overall survival, prostate-specific antigen (PSA) response, safety, curcumin absorption, and quality of life were investigated. An interim analysis was planned in the modified intention-to-treat population with data at 6 months (22 patients per arm). RESULTS: Despite good compliance and a verified absorption of curcumin, no difference was shown for our primary endpoint: progression-free survival (PFS) between the placebo and curcumin groups was, respectively, 5.3 months versus 3.7 months, p = 0.75. Similarly, no difference was observed for the secondary objectives: PSA response rate (p = 0.88), overall survival (p = 0.50), and quality of life (p = 0.49 and p = 0.47). CONCLUSION: Even though our previous studies and data in the literature seemed to support an association between curcumin and cancer therapies in order to improve patient outcome and prognosis, the results from this interim analysis clearly showed that adding curcumin to mCRPC patients' treatment strategies was not efficacious. The study was discontinued on the grounds of futility.

A Retrospective Study on the Onset of Menopause after Chemotherapy: Analysis of Data Extracted from the Jean Perrin Comprehensive Cancer Center Database Concerning 345 Young Breast Cancer Patients Diagnosed between 1994 and 2012.

OBJECTIVE: Young breast cancer (BC) patients receiving chemotherapy are at risk of chemotherapy-induced menopause (CIM). We sought to define the incidence rate of premature menopause after chemotherapy and to retrospectively investigate factors related to the onset of menopause. METHODS: We identified BC patients who had received chemotherapy at the Cancer Center (Centre Jean-Perrin). We selected premenopausal women aged between 18 and 50 years at the moment of diagnosis who received chemotherapy between 1994 and 2012. RESULTS: Of the 345 selected patients, the median age was 42 years (interquartile range: 38-46). CIM was defined as amenorrhea for at least 2 years following the end of chemotherapy. A total of 260 premenopausal women versus 85 menopausal women were included. Among the 85 menopausal women, only 46 were in the CIM group (13.3%). This rate increased in the group of women aged >43 years at diagnosis and with early hot flushes. CONCLUSION: CIM occurred in 13.3% of BC patients after chemotherapy. Age >43 years and early hot flushes were significantly associated with the risk of CIM. We suggest that the definition of CIM should be standardized in the literature: "amenorrhea of at least 2 years" seems a good cutoff, although 2 patients recovered their menstrual cycles beyond this limit.

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study.

OBJECTIVES: Favorable phase I results justified this pilot phase II study to assess the efficacy of docetaxel/curcumin in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC). METHODS: Thirty patients with progressing CRPC and a rising prostate-specific antigen (PSA) received docetaxel/prednisone in standard conditions for 6 cycles in combination with per os curcumin, 6,000 mg/day (day -4 to day +2 of docetaxel). The co-primary endpoint was the overall response rate determined by PSA and target assessments. An ancillary study assessed the seric values of chromogranin A (CgA) and neuron-specific enolase (NSE). RESULTS: Twenty-six patients received the scheduled treatment, 2 progressed and 2 died before the end of treatment. A PSA response was observed in 59% of patients (14% of PSA normalization) and achieved within the first three cycles for 88% of responders. Partial response was reached for 40% of evaluable patients. The regimen was well tolerated, and no adverse event was attributed to curcumin. Twenty patients were 100% curcumin compliant. The PSA level and objective response rate were not correlated with the serum values of CgA and NSE. CONCLUSION: This study produced additional data on curcumin as a treatment for cancer, with a high response rate, good tolerability and patient acceptability, justifying the interest to conduct a randomized trial.

Long-term dietary supplementation with cystathionine improves tissue glutathione in ageing rats.

BACKGROUND: Ageing is associated with decrease in tissue glutathione that can be reduced by food fortification with the amino acid cysteine. However, cysteine is not stable in solution and generates bad taste. Cystathionine, the direct precursor of cysteine, could be a valuable alternative. AIMS: This study aimed to determine whether long-term dietary supplementation with cystathionine induces an increase in glutathione pools. METHODS: Aged rats (20.5-month-old) were fed ad libitum during 29 weeks with either a cystathionine-supplemented diet (7.3 g/kg, n = 90 rats) or a control iso-nitrogenous alanine-supplemented diet (2.9 g/kg, n = 90 rats). RESULTS: Cystathionine was detected in the plasma of the cystathionine-supplemented rats but not in the control alanine-supplemented rats. Cystathionine increased glutathione concentrations in liver, small intestine and gastrocnemius muscle (P < 0.03). No adverse effect was observed. CONCLUSION: Cystathionine supplementation being able to increase moderately glutathione in healthy old rats could be considered as a candidate for nutritional supports aiming to revert the stronger glutathione depletions occurring in unhealthy elderly.