It has been clearly shown that androgen deprivation therapy (ADT) for the treatment of prostate cancer leads to loss of bone mineral density (BMD) and increased fracture risk. More importantly, loss of BMD shortens survival time. (see my post of December 27, 2009 “On the Horizon – Dasatinib A Drug to Inhibit the growth of Prostate Cancer in Bone and to Protect Bones from Osteolysis – Extending Life.”
Kuo, etal. hypothesize that intermittent ADT (IADT) may moderate BMD loss, thus decreasing fracture risk and extending life.
To confirm the positive effect of IADT on BMD they took men with rising PSA after surgery (RP) or radiation (RT) and put them on an IADT trial. After 9 months “on treatment” with leuprolide and flutamide, ADT was stopped and monthly PSA levels were measured during the “off treatment” interval until a threshold PSA (1 ng/mL for RP, 4 ng/mL for RT) was met. At these thresholds, ADT was resumed in another cycle and patients were treated intermittently in this manner until the prostate cancer became castration resistance.
Standardized average dual energy X-ray absorptiometry (DXA) scans (bone scans) of lumbar spine and left hip were performed at baseline and at each change in therapy. Men who completed at least one entire treatment cycle and who underwent at least 3 DXA scans were eligible for analysis.
Results: Forty-eight of 100 men met criteria. Mean spine BMD decreased 3.1% (p<0.0001) while mean hip BMD decreased 1.0% (p=0.005) during first "on treatment" interval. Significant gains were made in mean spine BMD of 1.8% (p=0.001) but not in the hip during first "off treatment" interval. Subsequent cycles of IADT also revealed attenuation of "on treatment" losses during "off treatment" intervals, though few achieved statistical significance. Despite regained BMD during "off treatment" intervals, the net result for the first cycle was loss of 1.3% (p=0.08) at the spine and 1.0% (p=0.02) at the hip.They concluded that ADT-induced loss of BMD is attenuated during the "off treatment" intervals of IADT. However, BMD does not return to baseline, sustaining only a smaller net loss. Might this effect survival time? It is possible, but they failed to follow up and obtain this information.To be presented at the 2010 ASCO Annual Meeting, Chicago, Ill. Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 4558) Abstract No: 4558 Author(s): E. Y. Yu, K. Kuo, R. Gulati, P. Y. Jiang, C. S. Higano; University of Washington, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; Providence Regional Cancer Partnership, Everett, WA; University of Washington School of Medicine, Seattle, WASee A similar study, with similar results, posted on this blog on April 20, 2010:
“Long-Term Effects of Intermittent Androgen Suppression on Testosterone Recovery and Bone Mineral Density: Results of a 33-Month Observational Study”
Joel T Nowak, MA, MSW