osteoporosis - prostate cancer

675 views

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
675
On SlideShare
0
From Embeds
0
Number of Embeds
116
Actions
Shares
0
Downloads
16
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide
  • This slide lists the disclosure information of the faculty and staff involved in the development of these slides.
  • Curatio PowerPoint Template 11/30/12 05:01 PSA, prostate specific antigen DRE, digital rectal exam TRUS, transrectal ultrasound
  • Curatio PowerPoint Template 11/30/12 05:01 Polling question – no right answer
  • Curatio PowerPoint Template 11/30/12 05:01 CORE
  • Curatio PowerPoint Template 11/30/12 05:01 Curatio PowerPoint Template Fact check: Data from table 2 in Shahinian (9112) NO PERMISSION NEEDED
  • Curatio PowerPoint Template 11/30/12 05:01
  • Curatio PowerPoint Template 11/30/12 05:01 There are many risk factors for bone loss in men, including age ≥ 65 years, prostate cancer itself, and hypogonadism (including ADT-induced hypogonadism) 1,2 References: Brown JP, Josse RG; Scientific Advisory Council of the Osteoporosis Society of Canada. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002;167(Suppl 10):S1-S34. Greenspan SL. Approach to the prostate cancer patient with bone disease. J Clin Endocrinol Metab 2008;93:2-7.
  • Curatio PowerPoint Template 11/30/12 05:01
  • Now, let’s move on to case two. This is an 80-year-old Caucasian gentleman with biochemically recurrent nonmetastatic prostate cancer, who started androgen deprivation therapy when his PSA got up to a level of 15. He had a DXA scan at baseline that revealed a T-score of -0.9 at the femoral neck of the left hip and -2.0 at the spine, so no osteoporosis or osteopenia. The patient, however, also has Crohn’s disease and is frequently put on steroid therapy to help manage his Crohn’s disease. He is a significant drinker by drinking 4 glasses of wine each day, and he also has a 60 pack/year history of cigarette smoking. He, however, has no history of fractures.
  • So again, the correct answers here are very similar to before. There is data with alendronate, there is data with denosumab, and there is data with zoledronic acid here in this setting. I think the key issue with this gentleman is that he does not have osteopenia or osteoporosis, as diagnosed by DXA scan, but he has a ton of risk factors. He has advanced age, steroid use, he drinks a significant amount of alcohol, he smokes, and of course he is on androgen deprivation therapy. He has many risk factors here, so I think the answers here—B would be fine, C would be fine. I think D might be overkill here at 120 mg subcu every 4 weeks. That was actually the FDA-approved dose for a man with metastatic castration-resistant prostate cancer to the bone for skeletal-related events. I think E is fine, with annual zoledronic acid. F was quarterly zoledronic acid. G—again, this is the zoledronic acid dose for men with metastatic castration-resistant disease to the bone. So, I would say here I certainly would do bone-targeted therapy. I don’t particularly like the answer A. I don’t like the answer of D or G here, but I think the other choices are all very reasonable.
  • Curatio PowerPoint Template 11/30/12 05:01
  • Curatio PowerPoint Template 11/30/12 05:01
  • Curatio PowerPoint Template 11/30/12 05:01
  • Curatio PowerPoint Template 11/30/12 05:01
  • Curatio PowerPoint Template 11/30/12 05:01 Mean Percent Changes from Baseline Bone Mineral Density (BMD) Values during the Study Period, According to Skeletal Site and Study Group. Results are presented as least-squares means of the BMDs of the lumbar spine (Panel A), the total hip (Panel B), the femoral neck (Panel C), and the distal third of the radius (Panel D). All values shown were significantly higher in the denosumab group than in the placebo group (P≤0.001). The means were estimated with the use of analysis-of-covariance models adjusting for study group, stratification variables, baseline BMD value, densitometer type, and the interaction between baseline BMD value and densitometer type. The means are based on data for 734 patients in each of the two groups except for the distal third of the radius, for which data were available for 161 patients in the denosumab group and 148 patients in the placebo group. I bars indicate 95% confidence intervals.
  • Now, what about fracture data? You can see here the bar graphs on the left, middle, and right, looking at 1, 2 and 3 years are all statistically significant in favor of denosumab, with less for osteoporotic fractures compared with placebo.
  • Curatio PowerPoint Template 11/30/12 05:01
  • osteoporosis - prostate cancer

    1. 1. Preventing Osteoporotic Fractures in Men With Early-Stage Prostate Cancer Michael A. Carducci, MD AEGON Professor in Prostate Cancer Research Johns Hopkins Kimmel Cancer Center Baltimore, MarylandThis program is supported by an educational donation from
    2. 2. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com)DisclaimerThe materials published on the Clinical Care Options Web site reflect the views of the authors of theCCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providingeducational grants. The materials may discuss uses and dosages for therapeutic products that have notbeen approved by the United States Food and Drug Administration. A qualified healthcare professionalshould be consulted before using any therapeutic product discussed. Readers should verify all informationand data before treating patients or using any therapies described in these materials.
    3. 3. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Disclosure Michael A. Carducci, MD, has disclosed that he has received consulting fees from Amgen, Bristol-Myers Squibb, and Novartis.
    4. 4. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Case 1  68-yr-old retired truck driver  High blood pressure; diabetes, noninsulin requiring  BMI: 32 (obese); nonsmoker; alcohol intake: 2-3 beers/day  Presents with PSA 50  DRE clinical stage T3b  TRUS: biopsies with Gleason 4 + 3 in 9 of 12 cores  No detectable metastases by bone scan and CT  After discussing options, patient decides on external beam radiation therapy + 3 yrs of ADT
    5. 5. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Would you recommend additional therapy to prevent bone loss/fractures? A. No, since I did not get a baseline BMD B. Yes, regardless of baseline BMD C. Yes, but only if he is osteoporotic D. Yes, if he is osteopenic or osteoporotic
    6. 6. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology ADT-Associated Bone Loss Healthy men[1] 0.5% Late menopausal women[1] 1.0% Early menopausal women[1] 2.0% AI therapy in postmenopausal women[2] 2.6% Bone marrow transplant[3] 3.3% Androgen deprivation therapy[4] 4.6% AI therapy + GnRH agonist[5] 7.0% Ovarian failure 7.7% secondary to chemotherapy[6] 0 2 4 6 8 Lumbar Spine BMD Loss at 1 Yr (%)1. Kanis JA. Osteoporosis. Blackwell Healthcare Communications Ltd; 1997. 2. Eastell R, et al. J BoneMineral Res. 2002;17(suppl 2). Abstract 1170. 3. Lee WY, et al. J Clin Endocrinol Metab. 2002;87:329-335. 4. Maillefert JF, et al. J Urol. 1999;161:1219-1222. 5. Gnant M. Breast Cancer Res Treat. 2002;76(suppl 1):S31. Abstract 12. 6. Shapiro CL, et al. J Clin Oncol. 2001;19:3306-3311.
    7. 7. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Proportion of Patients With Fractures 1-5 Yrs After Cancer Diagnosis +6.8%; P < .001 21 No ADT (n = 20,035) ADT (n = 6650) 18 19.4 15 Frequency (%) 12 12.6 9 +2.8%; P < .001 6 5.2 3 2.4 0 Any Fracture Fracture Resulting in HospitalizationShahinian VB, et al. N Engl J Med. 2005;352:154-164.
    8. 8. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Fractures Impact Mortality and Life Expectancy  Hip fracture – Affects life expectancy dramatically[1,2] – Aged 60-69 yrs: 11.5 yrs of decreased life expectancy – Aged 0-79 yrs: 5.0 yrs of decreased life expectancy  Vertebral facture – Prevalence in men is high (20%)[3] – Clinical consequences: pain, kyphosis, loss of height, respiratory problems [4,5] – 4 x increased risk of subsequent fracture[6] – Predict increased mortality in men with a 10-yr HR of 2.4 (95% CI: 1.6-3.9)[6,7]1. Cree M, et al. J Am Geriatr Soc. 2000;48:283-288. 2. Center JR, et al. Lancet. 1999;353:878-882. 3. O’Neill TW, et al. JBone Miner Res. 1996;11:1010-1018. 4. Matthis C, et al. Osteoporosis Int. 1998;8: 364-372. 5. Francis RM, et al. QJM.2004;97:63-74. 6. Johnell O, et al. Osteoporos Int. 2004;15:175-179. 7. Lau E, et al. J Bone Joint Surg Am. 2008;90:1479-1486. 8. Hasserius R, et al. Osteoporos Int. 2003;14:61-68.
    9. 9. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Screening for Bone Loss in Men: Who Is at Risk? Demographic Factors 65 yrs of age or older History Family history of osteoporotic fracture Fragility fracture after 40 yrs of age Significant height loss Lifestyle and Dietary Factors Smoking Excessive intake of alcohol or caffeine (> 4 cups/day) Inadequate dietary calcium intake Weight < 57 kg (or loss of > 10% of weight at 25 yrs of age) Physical Findings Vertebral deformity (eg, kyphosis) or osteopenia evident on x-ray Diseases Associated With Bone Loss Prostate cancer COPD Malabsorption syndrome Hyperparathyroidism Hyperthyroidism Hypogonadism Rheumatoid arthritis Renal insufficiency Vitamin D deficiency Treatments Associated With Bone Loss ADT Anticonvulsants Heparin Systemic glucocorticoids (duration > 3 mos) Entries in bold are considered major risk factors.Brown JP, et al. CMAJ. 2002;167:S1-S34. Greenspan SL. J Clin Endocrinol Metab. 2008;93:2-7.
    10. 10. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology The FRAX® Index: Assessing Fracture RiskAvailable at: http://www.sheffield.ac.uk/FRAX/. Image used with permission of the WHO CollaboratingCentre for Metabolic Bone Diseases, University of Sheffield. FRAX ® is registered to Professor JA Kanis,University of Sheffield.
    11. 11. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Case 2  80-yr-old male with biochemically recurrent, nonmetastatic prostate cancer starting ADT for a PSA of 15  5′9″ (175.3 cm), 158 lbs (72.1 kg)  DEXA scan at baseline reveals T-score of -0.9 at the femoral neck of the left hip and -0.2 at the spine  Patient also has Crohn’s disease and frequently receives steroid treatment  Drinks 4 glasses of wine/day and is a 60 pack-yr cigarette smoker  No previous history of fracture
    12. 12. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology In addition to lifestyle modification, would you also recommend bone-targeted therapy for this patient? A. No B. Yes, alendronate 70 mg/wk PO C. Yes, denosumab 60 mg SC q6m D. Yes, zoledronic acid 5 mg IV annually E. Yes, zoledronic acid 4 mg IV annually F. Yes, zoledronic acid 4 mg IV quarterly
    13. 13. Treatment Options
    14. 14. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Alendronate Increases BMD During GnRH Agonist Therapy 5 12-Mo Data 4 BMD Percent Change 3 Placebo 2 Alendronate 1 0 -1 -2 -3 Lumbar Total Spine HipGreenspan SL, et al. Ann Intern Med. 2007;146:416-424.
    15. 15. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Annual Zoledronic Acid Increases BMD During GnRH Agonist Therapy 6 Final 12-Mo Data P < .005 for each comparison 4 BMD Percent Change 2 Placebo Zoledronic acid 4 mg/yr IV 0 -2 -4 -6 Lumbar Total Spine HipMichaelson MD, et al. J Clin Oncol. 2007;25:1038-1042.
    16. 16. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Quarterly Zoledronic Acid Increases BMD During GnRH Agonist Therapy 8 Final 12-Mo Data P < .001 for each comparison 6 BMD Percent Change 4 Placebo Zoledronic acid 2 0 -2 -4 Lumbar Total Spine HipSmith MR, et al. J Urol. 2003;169:2008-2012.
    17. 17. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Denosumab Increased BMD at All Skeletal Sites 10 A. Lumbar Spine 10 B. Total Hip 8 8 From Baseline (%) From Baseline (%) Change in BMD Change in BMD 6 Denosumab 6 4 4 Denosumab Difference at 24 mos, 2 6.7 percentage points 2 Difference at 24 mos, 0 0 4.8 percentage points -2 Placebo -2 -4 -4 Placebo -6 -6 01 3 6 12 24 36 01 3 6 12 24 36 Mos Mos 10 C. Femoral Neck 10 D. Distal Third of Radius 8 8 From Baseline (%) From Baseline (%) Change in BMD Change in BMD 6 6 4 Denosumab 4 Denosumab 2 Difference at 24 mos, 2 0 3.9 percentage points 0 Difference at 24 mos, 5.5 percentage points -2 -2 Placebo Placebo -4 -4 -6 -6 01 3 6 12 24 36 01 3 6 12 24 36 Mos MosSmith MR, et al. N Engl J Med. 2009;361:745-755.
    18. 18. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Denosumab for Fracture Prevention 10 Denosumab Placebo New Vertebral Fracture (%) 8 P = .004 P = .004 P = .006 6 3.9 4 3.3 1.9 2 1.5 1.0 0.3 0 12 24 36 Patients Mos at Risk, n 13 2 22 7 26 10Smith MR, et al. N Engl J Med. 2009;361:745-755.
    19. 19. Maximizing Skeletal Integrity in Patients With Cancerclinicaloptions.com/oncology Conclusions  Osteoporosis and fractures are an important health problem in older men  ADT for prostate cancer increases risks for osteoporosis and fractures  Some but not all men require drug therapy to prevent fractures during ADT  Effective therapies are available – Bisphosphonates increase BMD – Denosumab increases BMD and decreases vertebral fractures
    20. 20. Go Online for More Education on Bone HealthInteractive Decision Support Tools: Experts make treatmentrecommendations for patients with prostate or breast cancerOptimizing Bone Health in Patients With Cancer: Proceedings of anIndependent Expert PanelDownloadable slidesclinicaloptions.com/oncology

    ×