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

Hedlund, Per Olov; Damber, Jan‐Erik; Hagerman, Inger; Haukaas, Svein A.; Henriksson, Peter; Iversen, Peter; Klarskov, Peter; Lundbeck, Finn; Rasmussen, Finn; Varenhorst, Eberhard; Viitanen, Jouko

doi:10.1080/00365590801943274

Cited by 58 publications

(42 citation statements)

References 25 publications

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“…Clinical studies comparing estrogen to other forms of ADT have shown that men treated with estrogen are less troubled by hot flashes (Spetz et al 2001, Hedlund et al 2008, Langley et al 2013. In SPCG-5, 70% of men receiving PEP were free of hot flashes compared to 26% of men receiving CAB.…”

Section: :8mentioning

confidence: 99%

“…In comparison to high-dose synthetic oral estrogens, LHRHa had the advantage of relative cardiovascular safety and less gynaecomastia, at the significant cost of more VMS and osteoporosis (Leuprolide Study Group 1984, Ockrim et al 2006, Hedlund et al 2008. These side effects ensured that interest in estrogen as an alternative continued.…”

Section: Past and Present Endocrine Treatments For Prostate Cancermentioning

confidence: 99%

“…Large RCTs of intramuscular polyestradiol phosphate (PEP), with median follow-up period of over 10 years, showed no overall mortality or cancer-specific survival difference compared with combined androgen blockade (CAB) (Hedlund et al 2008) or orchiectomy (Mikkola et al 2007). However, both the SPCG-5 trial (Hedlund et al 2008) and the Finnprostate 6 study (Mikkola et al 2007) demonstrated more cardiovascular morbidity in the PEP arm, without excess cardiovascular mortality in patients with metastatic disease.…”

Section: Past and Present Endocrine Treatments For Prostate Cancermentioning

confidence: 99%

“…However, both the SPCG-5 trial (Hedlund et al 2008) and the Finnprostate 6 study (Mikkola et al 2007) demonstrated more cardiovascular morbidity in the PEP arm, without excess cardiovascular mortality in patients with metastatic disease. However, in the Finnprostate 6 study, patients with locally advanced disease did experience a higher risk of cardiovascular death (RR 3.52; 95% CI 1.65-7.54; P = 0.001) (Mikkola et al 2007).…”

Section: Past and Present Endocrine Treatments For Prostate Cancermentioning

confidence: 99%

“…Skeletal events including fractures were measured as a secondary outcome in the SPCG-5 trial of intramuscular PEP compared with CAB (Hedlund et al 2008). After median follow-up of 11.7 years (10.1-13.7), 18 skeletal events including 9 femoral neck fractures and 7 spinal cord compressions had occurred in the CAB group (n = 455) and 0 had occurred in the PEP group (n = 455) (P = 0.001).…”

Section: Effect Of Estradiol On Bonementioning

confidence: 99%

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Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Russell

Cheung

Grossmann

2017

Endocrine-Related Cancer

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Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. Conventional endocrine treatment for PCa leads to global sex steroid deprivation. The ensuing severe hypogonadism is associated with well-documented adverse effects. Recently, it has become apparent that many of the biological actions attributed to androgens in men are in fact not direct, but mediated by estradiol. Available evidence supports a primary role for estradiol in vasomotor stability, skeletal maturation and maintenance, and prevention of fat accumulation. Hence there has been interest in revisiting estradiol as a treatment for PCa. Potential roles for estradiol could be in lieu of conventional androgen deprivation therapy or as low-dose add-back treatment while continuing androgen deprivation therapy. These strategies may limit some of the side effects associated with conventional androgen deprivation therapy. However, although available data are reassuring, the potential for cardiovascular risk and pro-carcinogenic effects on PCa via estrogen receptor signalling must be considered.

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Section: :8mentioning

confidence: 99%

Section: Past and Present Endocrine Treatments For Prostate Cancermentioning

confidence: 99%

Section: Past and Present Endocrine Treatments For Prostate Cancermentioning

confidence: 99%

Section: Past and Present Endocrine Treatments For Prostate Cancermentioning

confidence: 99%

Section: Effect Of Estradiol On Bonementioning

confidence: 99%

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Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Russell

Cheung

Grossmann

2017

Endocrine-Related Cancer

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Prostate Neoplasm

et al. 2019

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Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases

Varenhorst

Klaff

Berglund³

et al. 2016

Cancer Medicine

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Approximately 15% of men with hormone naïve metastatic prostate cancer primarily fail to respond to androgen deprivation treatment (ADT). The reason why the response to ADT differs in this subgroup of men with prostate cancer remains unclear. The aim of this study was to describe the characteristics of these men and to thereby define predictors of early ADT failure in prostate cancer patients with bone metastases. The study was based on 915 men from the prospective randomized multicenter trial (no. 5) conducted by the Scandinavian Prostate Cancer Group comparing parenteral estrogen with total androgen blockade. Early ADT failure was defined as death from metastatic prostate cancer within 12 months after the start of ADT. Multivariate logistic regression models were applied to identify clinical predictors of early ADT failure. Ninety‐four (10.3%) men were primarily nonresponders to ADT. Independent predictors of early ADT failure were poor Eastern Cooperative Oncology Group performance status (PS), analgesic consumption, low hemoglobin, and high Soloway score (extent of disease observed on the scan), in where patients with poor PS and/or high analgesic consumption had a threefold risk of early ADT failure. Not significantly factors related to early ADT failure were age, treatment, cardiovascular comorbidity, T category, grade of malignancy, serum estrogen level, and SHBG at enrolment. We analyzed characteristics of a subgroup of patients who primarily failed to respond to ADT. Four independent clinical predictors of early ADT failure could be defined, and men exhibiting these features should be considered for an alternative treatment.

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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

Cited by 58 publications

References 25 publications

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Prostate Neoplasm

Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases

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