Hedlund Per Olov, Johansson Robert, Damber Jan Erik, Hagerman Inger, Henriksson Peter, Iversen Peter, Klarskov Peter, Mogensen Peter, Rasmussen Finn, Varenhorst Eberhard
Department of Urology, Karolinska University Hospital Solna, Sweden.
Scand J Urol Nephrol. 2011 Nov;45(5):346-53. doi: 10.3109/00365599.2011.585820. Epub 2011 May 31.
This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin®) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease.
Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naïve prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin®) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl®) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression.
There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p < 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036).
Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e.g. avoidance of osteopenia and hot flushes and the low price, are given priority.
本研究旨在评估高剂量肠胃外磷酸多雌二醇（PEP，爱斯妥）或联合雄激素剥夺（CAD）治疗转移性前列腺癌患者期间心血管事件的预后风险因素，特别关注治疗前的心血管疾病。
915例T0 - 4、Nx、M1、G1 - 3、激素初治前列腺癌患者被随机分为两组，一组接受240mg PEP肌肉注射，每月两次，共2个月，之后每月一次；另一组接受氟他胺（福至尔）250mg口服，每日三次，联合曲普瑞林（达必佳）3.75mg每月肌肉注射，或根据选择进行双侧睾丸切除术。记录治疗前的心血管发病率，并由经验丰富的心脏病专家评估治疗期间的心血管事件。使用逻辑回归进行多变量分析。
既往有缺血性心脏病（p = 0.008）、缺血性脑疾病（p = 0.002）、间歇性跛行（p = 0.031）的患者，尤其是将所有治疗前有心血管疾病的患者作为一组进行分析时（p < 0.001），接受PEP治疗期间心血管事件显著增加。在该组中，33%的患者在PEP治疗期间发生了心血管事件。在多变量分析中，PEP是心脏并发症最重要的风险因素（p = 0.029）。即使在CAD组中，将所有既往有心血管疾病的患者作为一组分析时，心血管事件也显著增加（p = 0.036）。
既往有心血管疾病的患者在接受高剂量PEP治疗期间，甚至在CAD治疗期间，发生心血管事件的风险相当高。治疗前无心血管疾病的患者在PEP治疗期间有中度心血管风险，如果优先考虑这种治疗的优势，如避免骨质减少和潮热以及价格低廉，则可考虑采用这种治疗方法。
