Saad_edit.qxd 26/7/07 12:14 Page 24
Prostate Cancer
Figure 1: Treating Hormone-refractory Prostate Cancer
symptomatic.
12
Presently, zoledronic acid is the only bisphosphonate
that has shown efficacy in prostate cancer.
PSA or clinical progression
with castrate levels of The combination of docetaxel and zoledronic acid has demonstrated
testosterone
additive antitumour activity in a human prostate cancer cell line,
PC-3.
13
The antitumour activity of docetaxel was increased with the
addition of zoledronic acid in a dose-dependent manner. These results
Stop anti-androgens,
suggest that combination therapy with docetaxel and zoledronic acid
consider second-line
could be especially active in patients with HRPC.
14
hormonal manipulation
No evidence of Bone metastases Future Therapies
bone metastases present
Novel agents are also being investigated in this setting. Several
treatment modalities, such as the endothelin receptor antagonist
atrasentan, have shown activity in bone metastatic HRPC in a placebo-
No standard of care: controlled phase III trial. Although the study did not achieve its primary
clinical trials whenever
Asymptomatic Symptomatic
possible
end-point, in patients with bone metastases there was a significant
delay in progression in patients receiving atrasentan. Results from an
Zoledronic acid Zoledronic acid and
Regular scans for early
docetaxel (first choice) on-going phase III study in preventing metastases will further help in
detection of bone
Docetaxel or mitoxantrone
metastases. (Patients
defining the role of this agent in clinical practice. Vaccines, vitamin D
with rapid PSA doubling
analogues and antisense oligonucleotides are currently under
times at high risk.)
Palliative radiation as needed for localised
pain or to prevent impending fracture
investigation in the HRPC setting, but appear to show promising
results in phase II studies. Second-line therapy after primary
Note: Research is very important in the area of HRPC and clinical trials are encouraged
whenever possible. chemotherapy for HRPC is an active area of research. In patients who
respond to first-line docetaxel, it is reasonable to re-challenge with the
treatments for patients with bone metastases. Bisphosphonates are same agent. Other agents are presently being investigated in this
inhibitors of osteoclast-mediated bone resorption. They can prevent setting and, to date, satraplatin appears to show activity. Antisense
bone loss in patients with prostate cancer receiving ADT, and clusterin is presently being studied in the second-line setting in
zoledronic acid can increase bone mineral density in this setting.
9,10
combination with chemotherapy, given the promising pre-clinical
Zoledronic acid has demonstrated significant clinical benefits, proof of principle.
including the delay and prevention of skeletal complications and
durable pain palliation in patients with bone metastases from HRPC.
11
Conclusion
Moreover, bisphosphonates can be combined with chemotherapy. Advanced HRPC is a multifaceted problem and needs a
Indeed, zoledronic acid has been used safely with a variety of cytotoxic multidisciplinary approach. Urologists should remain involved from the
chemotherapies in clinical trials. Adverse events reported during time of diagnosis throughout the continuum of care, and should
bisphosphonate treatment did not appear to increase with be familiar with the new challenges that this disease presents.
concomitant chemotherapy. Medical oncologists will have to take up the challenge of being actively
involved in decision-making earlier than they have been used to in the
Based on the available evidence, several guidelines – including those of past. All specialities involved need to be aware that hormone therapy
the National Comprehensive Cancer Network, the European diminishes bone health, chemotherapy with docetaxel can provide a
Association of Urology and the International Consultation on survival benefit in HRPC, and zoledronic acid reduces and delays
Urological Diseases – recommend that bisphosphonates be used to skeletal complications. Building on these positive results is necessary to
preserve bone health and to prevent skeletal complications in patients further improve survival, symptom management and QoL in these
with bone metastases from HRPC, whether asymptomatic or poor-prognosis patients. ■
1. Preston DM, Torrens JI, Harding P, et al., Androgen deprivation mitoxantrone plus prednisone or prednisone alone for prostate cancer, N Engl J Med, 2001;345:948–55.
in men with prostate cancer is associated with an increased symptomatic hormone-resistant prostate cancer: a Canadian 11. Saad F, Gleason DM, Murray R, et al., Long-term efficacy of
rate of bone loss, Prostate Cancer Prostatic Dis, 2002;5:304–10. randomized trial with palliative endpoints, J Clin Oncol, zoledronic acid for the prevention of skeletal complications in
2. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS, Risk of fracture 1996;14:1756–64. patients with metastatic hormone-refractory prostate cancer,
after androgen deprivation for prostate cancer, N Engl J Med, 7. Petrylak DP, Tangen CM, Hussain MHA, et al., Docetaxel and J Natl Cancer Inst, 2004;96:879–82.
2005;352:154–64. estramustine compared with mitoxantrone and prednisone for 12. Carroll PR, Neal D, Scher H, et al., Management of
3. Diamond TH, Higano CS, Smith MR, et al., Osteoporosis in men advanced refractory prostate cancer, N Engl J Med, 2004;351: disseminated prostate cancer. In: Denis L, Bartsch G, Khoury S,
with prostate carcinoma receiving androgen-deprivation 1513–20. et al. (eds), Prostate Cancer: 3rd International Consultation on
therapy: recommendations for diagnosis and therapies, Cancer, 8. Tannock IF, de Wit R, Berry WR, et al., Docetaxel plus Prostate Cancer–Paris, Paris, France: Health Publications,
2004;100:892–9. prednisone or mitoxantrone plus prednisone for advanced 2003;251–84.
4. Weinfurt KP, Li Y, Castel LD, et al., The significance of skeletal- prostate cancer, N Engl J Med, 2004;351:1502–12. 13 Corey E, Brown LG, Quinn JE, et al., Zoledronic acid exhibits
related events for the health-related quality of life of patients 9. Smith MR, Eastham J, Gleason DM, et al., Randomized inhibitory effects on osteoblastic and osteolytic metastases of
with metastatic prostate cancer, Ann Oncol, 2005;16:579–84. controlled trial of zoledronic acid to prevent bone loss in men prostate, Clin Cancer Res, 2003;9:295–306.
5. Oefelein MG, Ricchiuti V, Conrad W, Resnick MI, Skeletal receiving androgen deprivation therapy for nonmetastatic 14. Ullen A, Lennartsson L, Harmenberg U, et al.,
fractures negatively correlate with overall survival in men with prostate cancer, J Urol, 2003;169:2008–12. Additive/synergistic antitumoral effects on prostate cancer cells
prostate cancer, J Urol, 2002;168:1005–7. 10. Smith MR, McGovern FJ, Zietman AL, et al., Pamidronate to in vitro following treatment with a combination of docetaxel
6. Tannock IF, Osoba D, Stockler MR, et al., Chemotherapy with prevent bone loss during androgen-deprivation therapy for and zoledronic acid, Acta Oncol, 2005;44:644–50.
24 EUROPEAN GENITO-URINARY DISEASE 2007
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100