Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation

Evan Y. Yu, Roman Gulati, Donatello Telesca, Peter Jiang, Stephen Tam, Kenneth J. Russell, Peter S. Nelson, Ruth Etzioni, Celestia S. Higano

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Abstract

Purpose: This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death. Patients and Methods: Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as ≥ two consecutive increasing PSA values while on ADT with castrate testosterone levels. Results: Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (≤ v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis. Conclusion: In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of ≤ 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis.

Original languageEnglish (US)
Pages (from-to)2668-2673
Number of pages6
JournalJournal of Clinical Oncology
Volume28
Issue number16
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

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Castration
Androgens
Prostatic Neoplasms
Recurrence
Prostate-Specific Antigen
Therapeutics
Prostatectomy
Radiation
Leuprolide
Flutamide
Testosterone

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation. / Yu, Evan Y.; Gulati, Roman; Telesca, Donatello; Jiang, Peter; Tam, Stephen; Russell, Kenneth J.; Nelson, Peter S.; Etzioni, Ruth; Higano, Celestia S.

In: Journal of Clinical Oncology, Vol. 28, No. 16, 01.06.2010, p. 2668-2673.

Research output: Contribution to journalArticle

Yu, Evan Y. ; Gulati, Roman ; Telesca, Donatello ; Jiang, Peter ; Tam, Stephen ; Russell, Kenneth J. ; Nelson, Peter S. ; Etzioni, Ruth ; Higano, Celestia S. / Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 16. pp. 2668-2673.
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abstract = "Purpose: This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death. Patients and Methods: Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as ≥ two consecutive increasing PSA values while on ADT with castrate testosterone levels. Results: Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (≤ v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95{\%} CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95{\%} CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis. Conclusion: In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of ≤ 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis.",
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T1 - Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation

AU - Yu, Evan Y.

AU - Gulati, Roman

AU - Telesca, Donatello

AU - Jiang, Peter

AU - Tam, Stephen

AU - Russell, Kenneth J.

AU - Nelson, Peter S.

AU - Etzioni, Ruth

AU - Higano, Celestia S.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Purpose: This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death. Patients and Methods: Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as ≥ two consecutive increasing PSA values while on ADT with castrate testosterone levels. Results: Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (≤ v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis. Conclusion: In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of ≤ 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis.

AB - Purpose: This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death. Patients and Methods: Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as ≥ two consecutive increasing PSA values while on ADT with castrate testosterone levels. Results: Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (≤ v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis. Conclusion: In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of ≤ 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis.

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U2 - 10.1200/JCO.2009.25.1330

DO - 10.1200/JCO.2009.25.1330

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SP - 2668

EP - 2673

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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