title: Parenteral estrogen versus total androgen ablation in the treatment of advanced prostate carcinoma: effects on overall survival and cardiovascular mortality. The Scandinavian Prostatic Cancer Group (SPCG)-5 Trial Study.
abstract: OBJECTIVE
  To compare the effect on overall survival of total androgen ablation (TAA) with that of parenteral estrogen and to pay special attention to cardiovascular mortality. TAA (orchiectomy or a luteinizing hormone-releasing hormone analogue combined with an antiandrogen) has been proposed as superior to other endocrine treatments for patients with prostate carcinoma. Recently, the use of parenteral estrogen has been suggested to reduce or even negate the well-known cardiovascular side effects of oral estrogens.
  
  
  METHODS
  Nine hundred fifteen patients were randomized to intramuscular injections of 240 mg polyestradiol phosphate (PEP) every second week for the first 8 weeks (5 doses) followed by a maintenance dose of 240 mg every month (n = 458) or to bilateral orchiectomy or triptorelin 3.75 mg every month combined with the antiandrogen flutamide 250 mg three times daily. The choice between orchiectomy and triptorelin was at the discretion of the clinician and patient. Patients were stratified according to performance status, presence of cardiovascular disease, and alkaline phosphatase level. An observer totally unaware of the treatment given classified all deceased patients.
  
  
  RESULTS
  At a median follow-up of 18.5 months, no signs of a difference in overall survival were found between TAA and PEP (P <0.001). Of 458 patients, 266 (58.1%) had died in the PEP group compared with 269 (58.9%) of 457 patients in the TAA group. Within the TAA group, no difference in overall survival existed between patients who had undergone orchiectomy or who were given triptorelin. Furthermore, no differences in cardiovascular mortality were found (3.5% in the PEP group and 3.1% in the TAA group).
  
  
  CONCLUSIONS
  The current parenteral estrogen regimen seems to be of comparable efficacy and cardiovascular safety as TAA in terms of overall survival. PEP has by far the lowest drug cost and also the lowest cumulative direct costs and thus has the highest cost-effectiveness. We suggest that parenteral estrogen be included as a therapeutic option in the endocrine management of prostate carcinoma.
authors.affiliation: Department of Urology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: P O
authors.initials: PO
authors.lastname: Hedlund
authors.forename: P
authors.initials: P
authors.lastname: Henriksson
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000401:mortality; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D045166:Estradiol Congeners / Q000008:administration & dosage* / Q000009:adverse effects; D005485:Flutamide / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D017329:Triptorelin Pamoate / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D045166:Estradiol Congeners; D017329:Triptorelin Pamoate; D004958:Estradiol; D005485:Flutamide; D000469:Alkaline Phosphatase; C008958:polyestradiol phosphate