Polyestradiol Phosphate

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.

We determined how serial measurements of prostate specific antigen and alkaline phosphatase can be used to predict survival early in the course of hormone treated metastatic prostate cancer.

The study was based on a prospective randomized trial of 915 patients with metastatic prostate carcinoma designed to compare parenteral estrogen (polyestradiol phosphate) vs total androgen blockade. We included 697 men who survived at least 6 months and had complete serial measurements of prostate specific antigen and alkaline phosphatase. Six models were constructed based on prostate specific antigen and alkaline phosphatase at start, and after 6 months of treatment, alkaline phosphatase flare and relative prostate specific antigen velocity. We constructed time dependent receiver operating characteristic curves with corresponding area under the curve to predict death from prostate cancer within 3 years.

The best variables to predict outcome were alkaline phosphatase at 6 months (AUC 0.79 for polyestradiol phosphate and 0.72 for total androgen blockade), alkaline phosphatase at baseline (AUC 0.70 for polyestradiol phosphate and total androgen blockade) and prostate specific antigen at 6 months (AUC 0.70 for polyestradiol phosphate and total androgen blockade). Prostate specific antigen and alkaline phosphatase levels 6 months after start of treatment give better prediction of survival than baseline levels.

Alkaline phosphatase at start of treatment and alkaline phosphatase and prostate specific antigen after 6 months can be used to predict survival of hormone treated metastatic prostate cancer.