Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen

Henriksson, Peter; Carlström, Kjell; Pousette, Åke; Gunnarsson, Per Olov; Johansson, Charlotta; Eriksson, Birgitta; Altersgård-Brorsson, Ann Kristin; Nordle, Örjan; Stege, Reinhard

doi:10.1002/(sici)1097-0045(19990701)40:2<76::aid-pros2>3.0.co;2-q

Cited by 23 publications

(20 citation statements)

References 30 publications

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“…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.)…”

Section: Nature Of the Evidencementioning

confidence: 99%

“…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.)…”

Section: Nature Of the Evidencementioning

confidence: 99%

“…Pharmacokinetic studies suggest that a dose of at least 240 mg month À1 is required in order to produce sufficient oestradiol levels to rapidly suppress testosterone to castrate levels, in a manner similar to orchidectomy (Henriksson et al, 1999). Of the eight studies employing i.m.…”

Section: Nature Of the Evidencementioning

confidence: 99%

“…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.…”

Section: Nature Of the Evidencementioning

confidence: 99%

“…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).…”

Section: Nature Of the Evidencementioning

confidence: 99%

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

et al. 2008

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The objectives of this study were to assess the effectiveness and safety of parenteral oestrogen in the treatment of prostate cancer, and to examine any dose relationship. A systematic review was undertaken. Electronic databases, published paper and internet resources were searched to locate published and unpublished studies with no restriction by language or publication date. Studies included were randomised controlled trials of parenteral oestrogen in patients with prostate cancer; other study designs were also included to examine dose -response. Study selection, appraisal, data extraction and quality assessment were performed by one reviewer and independently checked by another. Twenty trials were included in the review. The trials differed with regard to the included patients, formulation and dose of parenteral oestrogen, comparator used, outcome measures reported and the duration of follow-up. The results provide no evidence to suggest that parenteral oestrogen, in doses sufficient to produce castrate levels of testosterone, is less effective than luteinising hormone-releasing hormone (LHRH) or orchidectomy in controlling prostate cancer, or that it is consistently associated with an increase in cardiovascular mortality. Further well-conducted trials of parenteral oestrogen are required. A pilot randomised controlled trial comparing transdermal oestrogen to LHRH analogues in men with locally advanced or metastatic prostate cancer is underway in the United Kingdom.

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Section: Nature Of the Evidencementioning

confidence: 99%

Section: Nature Of the Evidencementioning

confidence: 99%

Section: Nature Of the Evidencementioning

confidence: 99%

Section: Nature Of the Evidencementioning

confidence: 99%

Section: Nature Of the Evidencementioning

confidence: 99%

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

et al. 2008

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Endocrine treatment in prostate cancer

Denis¹,

Griffiths

2000

Semin. Surg. Oncol.

152

116

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Over its natural course, prostate cancer is a heterogeneous tumour with a generally slow but constant rate of growth. The androgen dependence of the prostate gland was demonstrated more than half a century ago by the landmark studies of Professor C. Huggins and colleagues. They established that androgens are implicated not only in growth regulation of the normal gland but also in the pathogenesis of prostate cancer, and that this malignant tissue retains some degree of androgen dependence. This concept was supported by studies of symptomatic clinical cancer, with androgen ablative therapy bringing relief to the patient in more than 80% of the cases. The classical treatment consisted of either bilateral orchiectomy, or administration of diethylstilbestrol (DES). Other forms of therapy followed, involving successive waves of new compounds that either withdrew androgen support from the cancer or blocked the androgens from their receptors in the prostate cancer cells. Chronologically, the progestagens can be well recognised, with one in particular: The successful derivative, cyproterone acetate (CPA). There also have been a number of oral vs. parenteral estrogens, the development of the luteinizing hormone‐releasing hormone agonists (LH‐RHA), the introduction of the non‐steroidal anti‐androgens characterised by flutamide and casodex, and more recently, the introduction of the LH‐RHA. Moreover, there have been multiple possible forms of combination treatment to obtain maximal androgen blockade (MAB). However, no major differences in treatment outcome have been reported during the last 5 decades and most treatment choices have been based on tradition, associated side effects, the preferences of a particular doctor and patient, together with economic considerations. Furthermore, endocrine treatment has never been shown to cure clinical prostate cancer, which consequently has led to initiatives to defer endocrine treatment or to use it intermittently or use it as a form of neo‐adjuvant or adjuvant treatment with surgery or radiotherapy. The history of endocrine therapy is replete with clinical trials that do not represent the patient population in general, and these trials share the clinical fact that they ignore the 20% to 30% of all patients who lack an initial response to a given endocrine treatment. Thus, it is no wonder that prognostic factors determine the outcome more than the treatment itself. Important to current endocrine treatment, however, is the shift to earlier stages of prostate cancer at initial diagnosis. Integration of endocrine treatment at this earlier phase in the pathogenesis of prostate cancer will substantially alter the treatment strategy in relation to long‐term benefit with regard to survival, associated side effects, and costs. This complex adjustment is enhanced by recent discoveries in the molecular biology of the prostate which show, on the one hand, that the dihydrotestosterone‐androgen receptor (DHT‐AR) complex is important in the regulation of gene expression, but also that a nu...

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