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Independently of absolute BMI values, the amount, onset date, and duration of early body weight gain may influence cardio-metabolic health later in adulthood. Values of cardiac and metabolic variables from a cohort study of morbidly obese patients were retrospectively analyzed to study the association between early weight history and metabolic syndrome (MetS) occurrence in adults. Of 950 patients with severe morbid obesity (age 44.3 ± 13.8 y, BMI 42.5 ± 7.0 kg/m2), 31.4% had started excess weight gain in childhood (CH), 19.9% in adolescence (ADO), and 48.7% in adulthood (AD). Despite different BMI values, MetS prevalence (57.8%) was not significantly different in the three groups (54.4% CH vs. 57.7% ADO vs. 59.8% AD, p = 0.59). The overweight onset period was not significantly associated with the development of MetS in adults (ADO: OR = 1.14 [0.69–1.92], p = 0.60; AD: OR = 0.99 [0.62–1.56], p = 0.95) despite a higher BMI in the early obesity onset group. Weight gain of more than 50% after age 18 years significantly increased the risk of MetS (OR = 1.75 [1.07–2.88], p = 0.026). In addition to crude BMI values, analysis of body mass trajectories is a relevant clinical tool in the assessment of metabolic risk, suggesting that the magnitude of weight gain may be more important for metabolic syndrome progression than the period of obesity onset.

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.

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. This study aimed to determine whether long-term dietary supplementation with cystathionine induces an increase in glutathione pools. 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). 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

The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under- or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects. Following a literature search on PubMed, studies on TKIs and their pharmacokinetic characteristics, plasma quantification and inter-individual variability was studied. TDM is commonly used in various medical fields, including cardiology and psychiatry, but is not often applied in oncology. Plasma concentration monitoring has been thoroughly studied for imatinib, in order to evaluate the usefulness of TDM. The measurement of plasma concentration can be performed by various analytical techniques, with liquid chromatography-mass spectrometry being the reference method. This method is currently used to monitor the efficacy and tolerability of imatinib treatments. Although TDM is already being used for imatinib, additional studies are required in order to improve this practice with the inclusion of other TKIs.

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.

Background: Everolimus (Afinitor®) plus exemestane are indicated for hormone receptor-positive, HER2/neu-negative metastatic breast cancer (MBC), in menopausal women without symptomatic visceral disease after recurrence or progression following aromatase inhibitors. But everolimus efficacy as late treatment has not been explored. Methods: Sixty-three MBC patients progressing under hormonotherapy (HT; n = 30) or after chemotherapy (CT; n = 32) received everolimus plus HT (EHT) and were analyzed for safety, efficacy and overall survival (OS). This cohort was compared with our previous 530 MBC patients stratified by line (PMID 21852136). Results: The median duration of EHT was 27.8 weeks at 5-10 mg/day until clinical progression or toxicity. Median OS was not reached (median follow-up 18 months). Twelve-month survival was 100, 79 and 49% for patients treated with 0 (n = 13), 1-2 (n = 18) and >3 CT (n = 32), respectively. Median time-to-treatment failure was 6.4 months. In 62 EHT patients randomly matched 1:7 with 421 previous patients for age and number of CT, OS improved compared with patients receiving a new CT (p = 0.062). In patients pretreated with Conclusions: These results may support the use of EHT whatever the number of previous lines.

e11526 Background: Everolimus, in combination with exemestane, is indicated to treat hormone receptor-positive, HER2-negative metastatic breast cancer (MBC), in postmenopausal women without symptom...

e16021 Background: Prostate cancer is a major problem in the aging male population. Docetaxel, the first-line reference treatment in CRPC induces a prostate-specific antigen (PSA) response in 45% of patients and an objective tumor response in 12%. Preclinical studies suggested that curcuminoids inhibit tumor metastasis, invasion and angiogenesis and reverse drug resistance. We wanted to potentiate docetaxel by curcuminoïds in CRPC first line. Our previous phase I study showed the safety and the tolerability of CCM associated to docetaxel for advanced breast cancers. We have conducted in 2009-2010 a phase II study to assess the response of CRPC to this combination. Methods: Patients (n=30) with progressing CRPC and rising PSA were enrolled to receive the experimental treatment. Docetaxel was given in standard conditions (75mg/m², 1h i.v infusion every 3 weeks for 6 cycles + prednisolone) with CCM orally at the dose of 6gr/day (7 days by cycle: d-4 to d+2). The primary endpoint was response rate assessed by biological and paraclinical examinations. The secondary endpoints included safety, time to progression and compliance. Twenty nine patients were evaluable on PSA assessment and 15 on RECIST criteria. Results: 26 patients received the treatment totality and 4 withdrew prematurely. No patient withdrew for toxicity (2 deaths and 2 PSA progressions). A PSA response was observed in 17/29 patients (59%) (4 complete and 13 partial) observed rapidly (before the 3rd cycle) for 15 patients. The median time to subsequent PSA progression (TTP) was 5.8 months. Six patients (40%) had a partial objective response and 9 (60%) a stable disease. The median TTP on targets was 7.85 months (n=13/15). The regimen was well tolerated, with uncommon grade 3/4 toxicity; no adverse event was attributed to CCM. Of 169 cycles, 150 (89%) were completed with perfect compliance. Overall survival was 19 months (mean) and 24 months (median) with 17 events as of december 2012. Conclusions: These results are promising in improving the response rate to docetaxel in terms of both PSA decrease and objective response, with good tolerability and acceptability of CCM. A randomized trial is necessary to confirm this results. Clinical trial information: NCT01012141.