Parenteral polyoestradiol phosphate vs orchidectomy in the treatment of advanced prostatic cancer. Efficacy and cardiovascular complications: a 2‐year follow‐up report of a national, prospective prostatic cancer study

Abstract

Objective To evaluate the clinical efficacy and cardiovascular complications of orchidectomy or polyoestradiol phosphate (PEP) in the treatment of advanced prostatic cancer. Patients and methods In a prospective, randomized study 444 patients (mean age 73 years, range 45–91) with T3–4 M0 or T1–4 M1 prostatic cancer were treated either by orchidectomy (group 1, n=217) or parenteral PEP (group 2, n=227; 240 mg/month). The patients were examined at 3 and 6 months after start of the therapy and thereafter every 6 months; they were also assessed whenever they had symptoms indicating progression. Possible cardiovascular complications included myocardial infarction, cerebrovascular accident, pulmonary embolism and deep vein thrombosis. Results After a follow‐up of 2 years there was no statistically significant difference between the groups in progression‐free time; 65 of 217 (30%) patients in group 1 showed evidence of progression, including seven (3%) who died from prostate cancer. In group 2, 64 of 227 (28%) patients showed progression and eight (3.5%) died from prostatic cancer. There were 10 (5%) cardiovascular complications in patients in group 1, including five (2%) cardiovascular deaths; in group 2 there were 24 (11%) and 14 (6%), respectively. During the first year of treatment there were three (1.4%) cardiovascular complications in group 1 and 14 (6%) in group 2 (P<0.05), and during the second year, seven (4%) and 10 (6%), respectively. Conclusion Parenteral PEP (240 mg/month) seems to be as efficient as orchidectomy in inhibiting disease in patients with advanced prostatic cancer (T3–4 M0 and T1–4 M1). There were more cardiovascular complications in patients treated with PEP than after orchidectomy; the difference was statistically significant during the first year of treatment.

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

“…Therapies and routes of administration Of the 17 studies included in the review of effectiveness and safety, parenteral oestrogen was given alone in 9 studies with a total of 2192 patients (Jacobi et al, 1980;Steg et al, 1983;Bishop et al, 1989;Haapiainen et al, 1990;Aro et al, 1993;Lukkarinen and Kontturi, 1994;Mikkola et al, 1998;Henriksson et al, 1999;Hedlund et al, 2002), combined with oral oestrogen in 7 studies with a total of 1247 patients (Andersson et al, 1980;Daehlin et al, 1986;Haapiainen et al, 1986;Henriksson and Edhag, 1986;Aro et al, 1988;Johansson et al, 1991a;Lundgren et al, 1995), and combined with doxorubicin in 1 study with 188 patients (Leaf et al, 2003). Intramuscular (i.m.)…”

“…Intramuscular (i.m.) polyoestradiol phosphate (PEP) was used in 14 of the 17 included studies (Andersson et al, 1980;Daehlin et al, 1986;Haapiainen et al, 1986Haapiainen et al, , 1990Henriksson and Edhag, 1986;Aro et al, 1988Aro et al, , 1993Bishop et al, 1989;Johansson et al, 1991a;Lukkarinen and Kontturi, 1994;Lundgren et al, 1995;Mikkola et al, 1998;Henriksson et al, 1999;Hedlund et al, 2002), and 7 of the 9 studies using parenteral oestrogen alone (Bishop et al, 1989;Haapiainen et al, 1990;Aro et al, 1993;Lukkarinen and Kontturi, 1994;Mikkola et al, 1998;Henriksson et al, 1999;Hedlund et al, 2002). The other studies used intravenous (i.v.)…”

“…Of the eight studies employing i.m. parenteral oestrogen alone, three used PEP doses of 240 mg month À1 (Mikkola et al, 1998;Henriksson et al, 1999;Hedlund et al, 2002), while the remainder employed 160 mg month À1 (Bishop et al, 1989;Haapiainen et al, 1990;Aro et al, 1993;Lukkarinen and Kontturi, 1994) or 100 mg month À1 (Jacobi et al, 1980). Seven studies combined PEP at 80 mg month À1 with oral ethinyl oestradiol at 150 mg day À1 (Andersson et al, 1980;Daehlin et al, 1986;Haapiainen et al, 1986;Henriksson and Edhag, 1986;Aro et al, 1988;Johansson et al, 1991a;Lundgren et al, 1995), and the remaining study that assessed parenteral oestrogen in combination used 1 g Stilboestrol i.v.…”

“…It shows the variation in the patient populations between the studies, for example, all patients in the Hedlund trial had metastatic disease (Hedlund et al, 2002), compared with 45% in the Mikkola trial (Mikkola et al, 1998) and 12% in the Henriksson trial (Henriksson et al, 1999).…”

“…This study randomised patients with T0-4 NX M1 prostate cancer to either PEP twice a month for 2 months and thereafter monthly, or to combined androgen blockade (flutamide and LHRH analogue or on an optional basis bilateral orchidectomy). A second study (n ¼ 444), by Mikkola et al (2007Mikkola et al ( , 1998, randomised patients with T3-4 M0 or T1-4 M1 prostate cancer to either PEP or orchidectomy, and this study was of reasonable quality. The third study was a small phase II study, which randomised patients with newly diagnosed advanced prostate cancer to either PEP or orchidectomy (Henriksson et al, 1999).…”