Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer -- Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.
OBJECTIVE
In the mid-1980s, interest in parenteral estrogen therapy for prostate cancer was renewed when it was found that it influenced liver metabolism only marginally and had very few cardiovascular side-effects. In this study high-dose polyestradiol phosphate (PEP; Estradurin) was compared to combined androgen deprivation (CAD) for the treatment of patients with metastatic prostate cancer. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular side-effects.


METHODS
A total of 917 patients with T0-4, NX, M1, G1-3 prostate cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter once a month or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg per month i.m. or, on an optional basis, bilateral orchidectomy. A total of 556 patients had died at the time of this analysis.


RESULTS
There was no difference between the treatment arms in terms of time to biochemical or clinical progression and overall or disease-specific survival. There was no increase in cardiovascular mortality in the PEP arm. The PEP group had a higher prevalence of cardiovascular disease prior to the study and a significantly higher incidence of non-fatal ischemic heart events and heart decompensation during the study.


CONCLUSIONS
PEP has an equal anticancer efficacy to CAD and does not increase cardiovascular mortality. Final evaluation of cardiovascular morbidity is awaiting further analysis and follow-up. PEP is considerably cheaper than CAD.
Hedlund
Per Olov
PO
Department of Urology, Karolinska Hospital, Stockholm, Sweden. krea@beta.telenordia.se
Ala-Opas
Martti
M
Brekkan
Einar
E
Damber
Jan Erik
JE
Damber
Lena
L
Hagerman
Inger
I
Haukaas
Svein
S
Henriksson
Peter
P
Iversen
Peter
P
Pousette
Ake
A
Rasmussen
Finn
F
Salo
Jaakko
J
Vaage
Sigmund
S
Varenhorst
Eberhard
E
D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced; D018450:Disease Progression; D004359:Drug Therapy, Combination; 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; D007275:Injections, Intravenous; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000628:therapy*; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000009:adverse effects
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D045166:Estradiol Congeners; D017329:Triptorelin Pamoate; D004958:Estradiol; D005485:Flutamide; C008958:polyestradiol phosphate