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

Yu, Evan Y.; Kuo, Kevin F; Gulati, Roman; Chen, Shu; Gambol, Teresa E; Hall, Suzanne P; Jiang, Peter; Pitzel, Peggy; Higano, Celestia S.

doi:10.1200/jco.2011.38.3745

Cited by 38 publications

(21 citation statements)

References 31 publications

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“…Prior studies have shown that the largest decline in bone mineral density occurs during the first ADT on-treatment period with substantial heterogeneity in subsequent cycles. (25) It is also possible that there were inaccuracies in the submission of the claims. Finally, it was not known which patients were receiving bisphosphonate therapy, which may have affected the fracture rate.…”

Section: Discussionmentioning

confidence: 99%

Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer

et al. 2016

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Importance Although intermittent androgen deprivation therapy (ADT) has not been associated with better overall survival in prostate cancer (PC), it has the potential for lower side effects. The incidence of long-term adverse health events has not been reported. Objective Given that older patients are more likely to suffer long-term complications from ADT, we examined long-term late events in elderly patients randomized to intermittent or continuous ADT. Our hypothesis was that late cardiovascular and endocrine events would be lower in patients on intermittent ADT. Design Linkage between patient trial data and corresponding Medicare claims. Setting Multicenter clinical trial. Participants Patients from S9346, a randomized SWOG trial of intermittent vs. continuous ADT in men with metastatic PC. Main Outcomes and Measures The main outcome was to identify long-term adverse health events by treatment arm. Patients were classified as having an adverse health event if they had any hospital claim – or at least 2 physician or outpatient claims at least 30 days apart – for any of the following diagnoses: ischemic and thrombotic events; endocrine events; sexual dysfunction, dementia and depression. To incorporate time from beginning of observation through evidence of an event, we determined the cumulative incidence of each event. Competing risks Cox regression was used, adjusting for covariates. Results In total, n=1134 eligible U.S.-based patients with metastatic PC were randomized to continuous vs. intermittent ADT on S9346. A total of 636 (56%) of trial participants had ≥1 year of continuous Medicare parts A & B coverage and no HMO participation. The median age was 71.3 years. The most common long-term events were hypercholesterolemia (31%) and osteoporosis (19%). The 10-year cumulative incidence of ischemic and thrombotic events differed by arm; 24% for continuous and 33% for intermittent ADT (Hazard Ratio=0.69, p=.02). There were no statistically significant differences by arm in any other adverse health events. Conclusions and Relevance Contrary to our hypothesis that intermittent ADT would reduce long-term health-related events compared to continuous ADT, we found that older men assigned to intermittent ADT had no apparent reduction in bone, endocrine, or cognitive events and an increased incidence of ischemic and thrombotic events.

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Section: Discussionmentioning

confidence: 99%

Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer

et al. 2016

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“…59 Intermittent therapy also shows potential benefits for maintenance of improved bone health as demonstrated by significant recovery of bone health by delaying BMD loss and essentially allowing BMD a chance to recover between on-and off-treatment phases. 107 Intermittent treatment also offers a significant reduction in cost. 103 Finally, it is possible that intermittent treatment may prolong the amount of time that LHRHa can control PCa by delaying onset of castration resistance, although results of the recent Salonen et al 106 study suggest otherwise, demonstrating that further research is needed.…”

Section: Management Strategiesmentioning

confidence: 99%

Luteinizing Hormone–Releasing Hormone Agonists: A Quick Reference for Prevalence Rates of Potential Adverse Effects

Walker

Tran

Robinson

2013

Clinical Genitourinary Cancer

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“…14 Recent studies indicated that intermittent ADT, which enables testosterone recovery, appeared to attenuate ADT-induced bone loss as the levels of testosterone recovered. 15,16 …”

Section: Introductionmentioning

confidence: 99%

Effect of Androgen Deprivation Therapy on Bone Mineral Density in a Prostate Cancer Cohort in New Zealand: A Pilot Study

Wang

Karunasinghe

Plank

et al. 2017

Clin Med Insights Oncol

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Introduction:Reduction in bone mineral density (BMD) is a common side effect of androgen deprivation therapy (ADT). We aimed to examine the cross-sectional and longitudinal variation in BMD and associated bone markers in patients with nonmetastatic prostate cancer (PCa) managed with and without ADT.Methods:Bone mineral density of the total body, lumbar spine, femoral neck, ultradistal forearm, and one-third distal radius was measured in 88 patients with PCa without bone metastases at baseline and at 6 months. Patients were categorized into 4 groups: (1) acute ADT (≤6 months), (2) chronic ADT (>6 months), (3) former ADT, and (4) no ADT (controls). Serum levels of bone metabolism markers, procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX), were also measured.Results:In the cross-sectional analysis, men receiving chronic ADT had significantly lower total body BMD as compared with former ADT users and men with no ADT. In longitudinal analysis, a significant reduction in ultradistal forearm BMD was observed in both acute and chronic ADT users after 6 months (4.08% and 2.7%, P = .012 and .026, respectively). A significant reduction in total body BMD was observed in acute ADT users (2.99%, P = .032). Former ADT users had a significant increase in both lumbar spine and femoral neck BMD (2.84% and 1.59%, P = .008 and .002, respectively). The changes in BMD were not significantly different between acute and chronic ADT users. In the cross-sectional analysis, higher levels of PINP and CTX were observed in acute and chronic ADT users than former ADT users or PCa controls. In longitudinal analysis, the level of serum PINP and CTX did not change significantly from baseline to 6 months in acute, chronic, and former ADT users, or PCa controls, and the percentage change did not differ among the 4 groups.Conclusions:Men on acute ADT had a similar rate of bone loss to men on chronic ADT. Reversibility in ADT-induced bone loss was observed in those who discontinued ADT. Serum levels of PINP and CTX were higher in acute and chronic ADT users and levels returned to the range of PCa controls when treatment was withdrawn.

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

Cited by 38 publications

References 31 publications

Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer

Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer

Luteinizing Hormone–Releasing Hormone Agonists: A Quick Reference for Prevalence Rates of Potential Adverse Effects

Effect of Androgen Deprivation Therapy on Bone Mineral Density in a Prostate Cancer Cohort in New Zealand: A Pilot Study

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