title: 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.
  
  
  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.
authors.affiliation: Department of Urology, Karolinska University Hospital Solna, Sweden. Krea@beta.telenordia.se
authors.forename: Per Olov
authors.initials: PO
authors.lastname: Hedlund
authors.forename: Robert
authors.initials: R
authors.lastname: Johansson
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Damber
authors.forename: Inger
authors.initials: I
authors.lastname: Hagerman
authors.forename: Peter
authors.initials: P
authors.lastname: Henriksson
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.forename: Peter
authors.initials: P
authors.lastname: Klarskov
authors.forename: Peter
authors.initials: P
authors.lastname: Mogensen
authors.forename: Finn
authors.initials: F
authors.lastname: Rasmussen
authors.forename: Eberhard
authors.initials: E
authors.lastname: Varenhorst
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000150:complications* / Q000453:epidemiology / Q000209:etiology*; D003131:Combined Modality Therapy; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects*; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D012307:Risk Factors; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D017329:Triptorelin Pamoate; D004958:Estradiol; D005485:Flutamide; C008958:polyestradiol phosphate