Table 3 Included studies assessing parenteral oestrogen in combination with oral oestrogen or doxorubicin (PEP+)

From: Parenteral oestrogen in the treatment of prostate cancer: a systematic review

Study

N

Comparator

Follow-up

All-cause mortality

Prostate cancer mortality

Cardiovascular adverse events

Study quality

PEP at 80 mg monthly plus oral ethinyl oestradiol at 150 μg daily (PEP+)a

 Lundgren et al (1995)

285

(1) Estramustine phosphate 280 mg b.i.d., p.o.

(2) Surveillance, endocrine treatment on progression

⩾9 years

PEP+: 35/66 (53.0%)

Estramustine: 40/74 (54.1%)

Surveillance: 53/88 (60.2%)

PEP+: 8/66 (12.1%)

Estramustine: 13/74 (17.6%)

Surveillance: 25/88 (28.4%)

Events leading to withdrawal:

PEP+: 37/66 (56.1%)

Estramustine: 30/74 (40.5%)

Surveillance: 11/88 (21.5%)

Large number of patients withdrawn and excluded from analysis. Recruitment to PEP+ arm terminated early due to high CVS event rate

 Haapiainen et al (1986, 1991)

277

Orchidectomy

5 years

PEP+: 101/146 (69.1%)

Orchidectomy: 86/131 (65.6%)

PEP+: 45/146 (30.8%)

Orchidectomy: 47/131 (35.9%)

CVS mortality:

PEP+: 35/146 (24.0%)

Orchidectomy: 24/131 (18.3%)

Inappropriate randomisation (by date of birth)

 Andersson et al (1980)

263

Estramustine phosphate 840 mg day−1 b.i.d., p.o.

⩾2 years

NR

NR

No significant difference between groups (values not reported)

Trial groups not clearly explained

 Aro et al (1988)

151

(1) Orchidectomy

(2) Radiotherapy 40 Gy (whole pelvis), 26 Gy (prostate) over 9 weeks including 3 weeks rest

4 years

PEP+: 16/50 (32.0%)

Orchidectomy: 23/56 (41.1%)

Radiotherapy: 9/45 (20.0%)

NR

PEP+: 18/50 (36.0%), 5 fatal (10%)

Orchidectomy: 13/56 (23.2%), 6 fatal (10.7%)

Radiotherapy: 6/45 (22.2%), 3 fatal (11.1%)

Inappropriate randomisation (date of birth)

 Johansson et al (1991a, 1991b)

150

Orchidectomy

7–10 years

(5 years for survival data)

PEP+: 54/74 (73.0%)

Orchidectomy: 54/76 (71.1%)

PEP+: 27/74 (36.5%)

Orchidectomy: 36/76 (47.4%)

PEP+: 36/74 (48.6%), 13 fatal (17.6%)

Orchidectomy: 13/76 (17.1%), 9 fatal (11.8%)

Inappropriate randomisation (date of birth)

 Henriksson and Edhag (1986); Henriksson and Johansson (1987)

91/100

Orchidectomy

⩾1 year

NR

NR

Major CVS events

PEP+: 13/53 (24.5%)

Orchidectomy: 0/47 (0%)

9 non-randomised patients included

 Daehlin et al (1986)

30

(1) Estramustine phosphate 9.2 mg kg−1 day−1 b.i.d., p.o

(2) Orchidectomy

6 months

NR

NR

PEP+: 1/10 (10%), 0 fatal (0%)

Estramustine phosphate: 3/10 (30%), 1 fatal (10%)

Orchidectomy: 0/10 (0%)

Insufficient information to assess

1 g Stilboestrol i.v. every 2 weeks plus 50 mg m − 2 doxorubicin every 3 weeks a

 Leaf et al (2003)

188

Doxorubicin 50 mg m−2 every 3 weeks

>5 years

Median survival:

PEP+: 8.5 months

Doxorubicin: 7.7 months

NR

PEP+: 13.5%, 1.4% fatal

Doxorubicin: 1.3%, 0% fatal

Insufficient information to assess

  1. CVS=cardiovascular system; N=number of patients; NR=not reported; PEP=polyoestradiol phosphate; PEP+=PEP combined with oral oestrogen.
  2. Studies are ordered by sample size within dosage categories.
  3. Since increased cardiovascular risk occurs primarily during the first 2 years of oestrogen therapy, where trials report CVS events for more than one follow-up period, those closest to 2 years are given.
  4. aIn some trials, participants may have had higher initial treatment doses or may have received other additional treatment. The dose given here is the routine dose given for the duration of the trial. Further details can be found in the full evidence tables (see Appendix 7 of CRD report).
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