Phase II study of transdermal estradiol in androgen-independent prostate carcinoma

Lisa B. Bland, Mark Garzotto, Thomas Deloughery, Christopher Ryan, Kathryn Schuff, Emily M. Wersinger, Dianne Lemmon, Tomasz (Tom) Beer

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

BACKGROUND. Oral estrogen therapy has activity in patients with hormone-naive and androgen-independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids "first pass" liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC. METHODS. Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24-hour patches replaced every 7 days). Serum prostate-specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals. RESULTS. Three of 24 patients (12.5%; 95% confidence interval [CI], 0-26%) had a confirmed PSA reduction > 50%. The Kaplan-Meier estimate of median time to disease progression was 12 weeks (95% CI, 4.6-19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (±95% CI) serum estradiol level increased from 17.2 pg/mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL (range, 334.6-586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed. CONCLUSIONS. In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors.

Original languageEnglish (US)
Pages (from-to)717-723
Number of pages7
JournalCancer
Volume103
Issue number4
DOIs
StatePublished - Feb 15 2005

Fingerprint

Androgens
Prostate
Estradiol
Carcinoma
Hot Flashes
Blood Coagulation Factors
Bone Remodeling
Confidence Intervals
Prostate-Specific Antigen
Testosterone
Estrogens
Hormones
Activated Protein C Resistance
Sex Hormone-Binding Globulin
Protein S
Factor VIII
Kaplan-Meier Estimate
Gonadal Steroid Hormones
Therapeutics
Serum

Keywords

  • Estradiol
  • Estrogen
  • Hormonal therapy
  • Prostate carcinoma
  • Transdermal

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of transdermal estradiol in androgen-independent prostate carcinoma. / Bland, Lisa B.; Garzotto, Mark; Deloughery, Thomas; Ryan, Christopher; Schuff, Kathryn; Wersinger, Emily M.; Lemmon, Dianne; Beer, Tomasz (Tom).

In: Cancer, Vol. 103, No. 4, 15.02.2005, p. 717-723.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND. Oral estrogen therapy has activity in patients with hormone-naive and androgen-independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids {"}first pass{"} liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC. METHODS. Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24-hour patches replaced every 7 days). Serum prostate-specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals. RESULTS. Three of 24 patients (12.5{\%}; 95{\%} confidence interval [CI], 0-26{\%}) had a confirmed PSA reduction > 50{\%}. The Kaplan-Meier estimate of median time to disease progression was 12 weeks (95{\%} CI, 4.6-19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (±95{\%} CI) serum estradiol level increased from 17.2 pg/mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL (range, 334.6-586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed. CONCLUSIONS. In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors.",
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T1 - Phase II study of transdermal estradiol in androgen-independent prostate carcinoma

AU - Bland, Lisa B.

AU - Garzotto, Mark

AU - Deloughery, Thomas

AU - Ryan, Christopher

AU - Schuff, Kathryn

AU - Wersinger, Emily M.

AU - Lemmon, Dianne

AU - Beer, Tomasz (Tom)

PY - 2005/2/15

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N2 - BACKGROUND. Oral estrogen therapy has activity in patients with hormone-naive and androgen-independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids "first pass" liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC. METHODS. Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24-hour patches replaced every 7 days). Serum prostate-specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals. RESULTS. Three of 24 patients (12.5%; 95% confidence interval [CI], 0-26%) had a confirmed PSA reduction > 50%. The Kaplan-Meier estimate of median time to disease progression was 12 weeks (95% CI, 4.6-19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (±95% CI) serum estradiol level increased from 17.2 pg/mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL (range, 334.6-586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed. CONCLUSIONS. In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors.

AB - BACKGROUND. Oral estrogen therapy has activity in patients with hormone-naive and androgen-independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids "first pass" liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC. METHODS. Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24-hour patches replaced every 7 days). Serum prostate-specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals. RESULTS. Three of 24 patients (12.5%; 95% confidence interval [CI], 0-26%) had a confirmed PSA reduction > 50%. The Kaplan-Meier estimate of median time to disease progression was 12 weeks (95% CI, 4.6-19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (±95% CI) serum estradiol level increased from 17.2 pg/mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL (range, 334.6-586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed. CONCLUSIONS. In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors.

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