Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.
OBJECTIVE
To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events.


METHODS
In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with 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 monthly, or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg i.m. per month or on an optional basis bilateral orchidectomy.


RESULTS
At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001).


CONCLUSIONS
PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.
Hedlund
Per Olov
PO
Department of Urology, Karolinska University Hospital Solna, Sweden. krea@beta.telenordia.se
Damber
Jan-Erik
JE
Hagerman
Inger
I
Haukaas
Svein
S
Henriksson
Peter
P
Iversen
Peter
P
Johansson
Robert
R
Klarskov
Peter
P
Lundbeck
Finn
F
Rasmussen
Finn
F
Varenhorst
Eberhard
E
Viitanen
Jouko
J
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000556:secondary; D002423:Cause of Death; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004967:Estrogens / Q000008:administration & dosage*; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
D000726:Androgen Antagonists; D004967:Estrogens; D004958:Estradiol; D005485:Flutamide; C008958:polyestradiol phosphate