Η επίδραση της θεραπείας με LHRH ανάλογο στην ελαστικότητα των αγγείων και στην λειτουργικότητα του ενδοθηλίου σε ασθενείς με καρκίνο του προστάτη

Objective To study the effect of androgen deprivation therapy with an LHRH analogue in arterial stiffness and endothelial function of peripheral arteries as a possible mechanism increasing their cardiovascular riskMaterial- Methods This pilot study is a prospective analysis of 32 patients with metastatic prostate cancer who received Maximal Androgen Blockade. We evaluated the endothelial function of brachial artery through ultrasound and measurement of Flow Mediated Dilatation (FMD) and we assessed the central arterial stiffness of the aorta by measuring Augmentation index (AIX) and velocity of the aortic pulse wave (PWV). The measurements were performed one day before starting treatment and then three months and six months after the initiation of treatment.Results PWV increased significantly by 8, 26% from three to six months of follow up (p=0,037). FMD was found slightly elevated from baseline to 6 months of follow up by 7, 18% (p>0, 99), but AI was increased significantly (15, 53%, p=0,007) at six months as compared with baseline measures. Glucose, LDL, Triglycerides were increased by 15, 23% (p=0,002) 14, 34% (p<0,001), and 13, 46 %( p<0,001) respectively at 6 months follow up and these values increased significantly between all other time points. HDL was decreased statistically significantly by 14, 56 %( p<0,001) during the follow up of 6 months.Conclusions We found that these agents cause changes in arterial stiffness of the aorta and the endothelial function of peripheral arteries and we proposed them as a possible mechanism of increasing their cardiovascular risk

Low doses of ketoconazole and prednisone in patients with castration resistant prostate cancer (CRPC): A retrospective study on 73 patients.

e16099 Background: The management of rising PSA in metastatic CRPC remains controversial. In Italy, abiraterone and enzalutamide are not at all approved in this setting of patients (pts). Ketoconazole is an inhibitor of adrenal androgen synthesis that has shown anti-tumor activity by interfering with C-17,20-lyase and could be used as secondary hormonal manipulation. In this retrospective study we report our experience with low doses of ketoconazole and prednisone in the treatment for CRPC. Methods: From March 2007 to March 2012, 73 pts with progressive CRPC who were previously treated with maximal androgen blockade received 200 mg ketoconazole orally 2 times daily, orally replacement prednisone (5 mg bid) and maintained LHRH-agonists. Overall, 40/73 (55%) pts had only bone metastases, 13/73 (18%) had nodal metastases, 20/73 (27%) both. Pts were monitored clinically and with serial PSA measurements every month. Partial biochemical response (PR) was defined as a >50% fall in PSA from baseline. Progressive disease (PD) was defined by objective disease progression or PSA increase of >50% above nadir or >25% above baseline. The endpoints of the study were biochemical response (BR), progression free survival (PFS), overall survival (OS) and adverse events assessment. Results: Median age was 74 (70-78) years; median baseline PSA was 33.09 (1.18-1348.8) ng/ml; median duration of the treatment was 5.05 (0-56.8) months. Twenty out 73 pts (27%) showed a decrease in PSA >50%, with a median duration of PSA response of 3.56 (1.17-33.58) months and 3 pts (4%) a PD. Fifty out 73 pts (68%) achieved a SD with an overall disease control (PR+SD) of 85%. PFS was 10 months for pts who achieved PR and 4 months for those with SD. Differences in PFS stratified according to site of metastases showed better prognosis in patients with only lymph nodes disease (p<0.05). Treatment with Ketoconazole was well tolerated and grades 3-4 toxicities occurred in only 3% of patients. Conclusions: Low-dose ketoconazole is an effective and well-tolerated treatment in pts with CRPC and should be considered in the subset of pts with low tumor burden and a rising PSA level despite maximal androgen blockade.