Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: Evaluation of cardiovascular events in a randomized trial

Abstract

Objective. 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. Material and methods. 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. Results. 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). Conclusions. 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.

Key Words::

• cardiovascular events
• cardiovascular risk factors
• combined androgen deprivation
• parenteral oestrogen therapy
• prostate cancer
• randomized multicentre trial
• skeletal metastases

Acknowledgements

Dr Arto Mikkola, Department of Urology, Helsinki University Hospital, is acknowledged for fruitful discussion. This study was financially supported by Ferring AB, Malmö, Sweden, Ferring Laegemidler A/S Copenhagen, Denmark, Pharmacia AB, Uppsala, Sweden, and Schering-Plough AB, Stockholm, Sweden.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.