Intermittent Versus Continuous Total Androgen Blockade in the Treatment of Patients with Advanced Hormone-Naive Prostate Cancer: Results of a Prospective Randomized Multicenter Trial

Leval, Jean de; Boca, Philippe; Youssef, Enis; Hubert, N.; Jeukenne, Michel; Seidel, Laurence; Bouffioux, C; Coppens, Luc; Bonnet, Pierre; Andrianne, Robert; Waltregny, David

doi:10.3816/cgc.2002.n.018

Cited by 115 publications

(81 citation statements)

References 27 publications

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“…14, 15 There have not been differences in efficacy, but there is evidence of less toxicity in patients treated with IAD. Recently, a large trial of IAD versus continuous ADT for men with biochemically recurrent prostate cancer after radiation revealed an equal…”

Section: Introductionmentioning

confidence: 99%

Long-Term Dynamics of Bone Mineral Density During Intermittent Androgen Deprivation for Men With Nonmetastatic, Hormone-Sensitive Prostate Cancer

Kuo

Gulati

et al. 2012

JCO

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A B S T R A C T PurposeTo investigate changes in bone mineral density (BMD) and fracture risk in men who received intermittent androgen deprivation (IAD) for nonmetastatic, hormone-sensitive prostate cancer. Patients and MethodsMen with prostate cancer who lacked radiographically detectable metastases were treated in a prospective trial of IAD. After 9 months of treatment with leuprolide and flutamide, androgen deprivation therapy (ADT) was stopped until prostate-specific antigen reached a threshold (1 ng/mL for radical prostatectomy; 4 ng/mL for radiation or primary ADT) for a new cycle. Dual-energy x-ray absorptiometry (DXA) scans were performed before starting ADT and subsequently with each change in therapy. At least two consecutive DXA scans were required for this analysis. Computed tomography, bone scintigraphy, and lumbar spine x-rays were performed at the beginning and end of each treatment period. ResultsFifty-six of 100 patients met criteria for this analysis. The median age at study entry was 64.5 years (range, 49.8 to 80.9 years). The average percentage change in BMD during the first on-treatment period was Ϫ3.4% (P Ͻ .001) for the spine and Ϫ1.2% (P ϭ .001) for the left hip. During the first off-treatment period (median, 37.4 weeks; range, 13.4 weeks to 8.7ϩ years), BMD recovery at the spine was significant, with an average percentage change of ϩ1.4% (P ϭ .002). Subsequent periods had heterogeneous changes of BMD without significant average changes. After a median of 5.5 years (range, 1.1 to 13.8ϩ) years on trial, one patient (1.8%) had a compression fracture associated with trauma. ConclusionPatients experienced the greatest average change in BMD during early treatment periods of IAD with a smaller average change thereafter. Fractures were rare.

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Section: Introductionmentioning

confidence: 99%

Long-Term Dynamics of Bone Mineral Density During Intermittent Androgen Deprivation for Men With Nonmetastatic, Hormone-Sensitive Prostate Cancer

Kuo

Gulati

et al. 2012

JCO

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“…The off-treatment duration reported in prospective phase iii trials ranged from 50% to 82% 12,13,17,19 . It was 73% in the pr.7 trial, a level higher than that reported in phase ii trials, in which patients spent a mean of 39% of their time off treatment 7 .…”

Section: Testosterone During Iadmentioning

confidence: 99%

Androgen Deprivation Therapy in Advanced Prostate Cancer: Is Intermittent Therapy the New Standard of Care?

Klotz

Toren

2012

Current Oncology

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Purpose: Intermittent androgen deprivation is increasingly used as an alternative to continuous life-long androgen deprivation therapy for men with advanced or recurrent prostate cancer. Recent Findings: Two recent phase III trials have clarified the benefits of intermittent therapy. The Canadian-led pr.7 trial in men with nonmetastatic disease and prostate-specific antigen recurrence after definitive local therapy showed that intermittent therapy resulted in survival equivalent to that with continuous therapy, with significant improvements in quality of life. Patients on intermittent therapy experienced improved bone health, fewer metabolic and hematologic disturbances, fewer hot flashes, and improved sexual function. In men with metastatic disease, the data are less clear. The long-awaited results of the Southwest Oncology Group 9346 trial, comparing intermittent with continuous therapy in metastatic disease, showed no difference in overall survival. Post hoc stratification analysis showed a worse outcome in patients with “minimal” metastatic disease, and no difference in those with widespread bone metastases. The significance of that observation is in dispute. The present review also addresses practical issues in the use of intermittent therapy, including patient selection, follow-up, and therapy cycling. Summary: The recent results of randomized clinical trials now establish that intermittent androgen deprivation therapy is an approach that should be considered the standard of care in most patients with nonmetastatic prostate cancer requiring hormonal therapy and in selected patients with metastatic disease. Key Points: (1) Level I evidence supports the oncologic equivalence of intermittent compared with continuous androgen blockade in men with biochemical failure. (2) Compared with continuous androgen deprivation, intermittent therapy demonstrates improved quality of life and fewer side effects. (3) Patient selection for intermittent therapy is important to maintain good oncologic results. (4) Monitoring of prostate-specific androgen response and duration of off-treatment intervals allow for stratification of patients by risk of progression.

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“…The clinical trial focused on men in biochemical recurrence after they had received radiotherapy for locally advanced prostate cancer and has been used as a guideline for several subsequent large, Phase III, randomized studies. [30][31][32][33][34][35] …”

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confidence: 99%

Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer

Bruchovsky¹,

Klotz²,

Crook³

et al. 2006

Cancer

118

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The impact of reduced‐intensity conditioning (RIC) on the outcomes of hematopoietic cell transplantation (HCT) from unrelated ‐donors (UD) remains to be determined. We therefore assessed 128 patients, aged 16 to 66 years, with acute leukemia (n = 105) or myelodysplastic syndrome (n = 23) in a UD‐HCT trial using RIC with busulfan, fludarabine, and antithymocyte globulin. Patients were transplanted with unmanipulated bone marrow (BM, n = 41) or mobilized peripheral blood mononuclear cells (M‐PB, n = 87) and received cyclosporine and methotrexate for graft‐versus‐host disease (GVHD) prophylaxis. After a median follow‐up of 26.7 months (range, 5.9−70.7 months) in surviving patients, 19 patients had died without progression/recurrence of underlying disease, giving a cumulative incidence of transplantation‐related mortality (TRM) of 17% (95% confidence interval, 11%–27%; 1‐year TRM, 14%). Graft failure (n = 7) and infections (n = 5) were the most common causes of TRM. Only three patients died due to GVHD (acute, one; chronic, two). Graft failure, which occurred in eight patients, showed a significant correlation with graft source (BM, 6/41 vs. M‐PB, 2/87; P = 0.009). Donor‐patient HLA‐disparity did not correlate with GVHD, 1‐year TRM, and graft failure. RIC containing antithymocyte globulin led to decreased GVHD‐associated, as well as overall, TRM after UD‐HCT. This trial is registered at http://www.clinicaltrials.gov as NCT00627666. Am. J. Hematol. 86:399–405,2011. © 2011 Wiley‐Liss, Inc.

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Intermittent Versus Continuous Total Androgen Blockade in the Treatment of Patients with Advanced Hormone-Naive Prostate Cancer: Results of a Prospective Randomized Multicenter Trial

Cited by 115 publications

References 27 publications

Long-Term Dynamics of Bone Mineral Density During Intermittent Androgen Deprivation for Men With Nonmetastatic, Hormone-Sensitive Prostate Cancer

Long-Term Dynamics of Bone Mineral Density During Intermittent Androgen Deprivation for Men With Nonmetastatic, Hormone-Sensitive Prostate Cancer

Androgen Deprivation Therapy in Advanced Prostate Cancer: Is Intermittent Therapy the New Standard of Care?

Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer

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