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International Journal of Clinical Oncology

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01-08-2010 | Original Article

A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer

Authors: Mohamed S. Zaghloul, Rimoun Boutrus, Hisham El-Hossieny, Yasser Abdel Kader, Inas El-Attar, Mohamed Nazmy

Published in: International Journal of Clinical Oncology | Issue 4/2010

Abstract

Background

Zoledronic acid treatment reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from breast, lung, and urologic cancers including prostate and renal cancer. The aim of this study was to evaluate the effect of zoledronic acid on SREs in patients with bone metastases from bladder cancer.

Patients and methods

Patients with bone metastases from bladder cancer who were receiving palliative radiotherapy were randomized to placebo or zoledronic acid (4 mg intravenous monthly) for 6 months.

Results

The patients (n = 40) were evenly distributed between the two treatment groups, and the baseline demographics of the two groups were similar. The follow-up varied from 8 to 65 weeks (median 24 weeks). Compared with patients receiving placebo, those receiving zoledronic acid had a lower mean incidence of SREs (2.05 ± 1.0 vs. 0.95 ± 0.9, respectively), and a larger proportion did not experience an on-study SRE (2 vs. 8 patients, respectively). Zoledronic acid also prolonged the median time to first SRE compared with the placebo (16 vs. 8 weeks, respectively). Multiple event analysis of SREs revealed that zoledronic acid decreased the risk of SRE development by 59% (hazard ratio 0.413). Zoledronic acid also increased the 1-year survival rate compared with placebo (36.3 ± 11.2 vs. 0%, respectively). Zoledronic acid was generally well tolerated in our patient population.

Conclusions

Zoledronic acid therapy decreased the incidence of SREs and improved the 1-year survival rate of patients with bone metastases from bladder cancer, potentially through its anticancer activity.

Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108CrossRefPubMed

Parkin DM (2008) The global burden of urinary bladder cancer. Scand J Urol Nephrol Suppl 218:12–20

Zaghloul MS (2006) Adjuvant radiation therapy for locally advanced bladder cancer. In: US Oncological Disease. Touch Briefings, London, pp 86–89

Miller LS (1977) Bladder cancer: superiority of preoperative irradiation and cystectomy in clinical stages B2 and C. Cancer 39:973–980CrossRefPubMed

Zaghloul MS (1996) Distant metastasis from bilharzial bladder cancer. Cancer 77:743–749CrossRefPubMed

Volkmer BG, Kuefer R, Bartsch GC Jr et al (2009) Oncological followup after radical cystectomy for bladder cancer—is there any benefit? J Urol 181:1587–1593 (discussion 1593)CrossRefPubMed

Rosen LS, Gordon D, Tchekmedyian NS et al (2004) Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer 100:2613–2621CrossRefPubMed

Rosen LS, Gordon D, Tchekmedyian S et al (2003) Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial—the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 21:3150–3157CrossRefPubMed

Rosen LS, Gordon D, Kaminski M et al (2003) Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 98:1735–1744CrossRefPubMed

10.

Saad F, Gleason DM, Murray R et al (2004) Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96:879–882CrossRefPubMed

11.

Cleeland CS, Ryan KM (1994) Pain assessment: global use of the brief pain inventory. Ann Acad Med Singapore 23:129–138PubMed

12.

Cook RJ, Lawless JF (2002) Analysis of repeated events. Stat Methods Med Res 11:141–166CrossRefPubMed

13.

Lipton A (2007) Treatment of bone metastases and bone pain with bisphosphonates. Support Cancer Ther 4:92–100CrossRefPubMed

14.

Saad F (2008) New research findings on zoledronic acid: survival, pain, and anti-tumour effects. Cancer Treat Rev 34:183–192CrossRefPubMed

15.

Saad F, Lipton A (2007) Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease. Semin Oncol 34:S17–S23CrossRefPubMed

16.

Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176CrossRefPubMed

17.

Weinfurt KP, Anstrom KJ, Castel LD et al (2006) Effect of zoledronic acid on pain associated with bone metastasis in patients with prostate cancer. Ann Oncol 17:986–989CrossRefPubMed

18.

Mystakidou K, Katsouda E, Parpa E et al (2005) Randomized, open label, prospective study on the effect of zoledronic acid on the prevention of bone metastases in patients with recurrent solid tumors that did not present with bone metastases at baseline. Med Oncol 22:195–201CrossRefPubMed

19.

Aviles A, Nambo MJ, Neri N et al (2007) Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma. Med Oncol 24:227–230CrossRefPubMed

20.

Zarogoulidis K, Boutsikou E, Zarogoulidis P et al (2009) The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis. Int J Cancer 125:1705–1709CrossRefPubMed

21.

Guise TA (2008) Antitumor effects of bisphosphonates: promising preclinical evidence. Cancer Treat Rev 34[Suppl 1]:S19–S24CrossRefPubMed

22.

Winter MC, Holen I, Coleman RE (2008) Exploring the anti-tumour activity of bisphosphonates in early breast cancer. Cancer Treat Rev 34:453–475CrossRefPubMed

23.

Wood J, Bonjean K, Ruetz S et al (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061CrossRefPubMed

24.

Tas F, Duranyildiz D, Oguz H et al (2008) Effect of zoledronic acid on serum angiogenic factors in patients with bone metastases. Med Oncol 25:346–349CrossRefPubMed

25.

Kunzmann V, Bauer E, Feurle J et al (2000) Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 96:384–392PubMed

26.

Santini D, Martini F, Fratto ME et al (2009) In vivo effects of zoledronic acid on peripheral gammadelta T lymphocytes in early breast cancer patients. Cancer Immunol Immunother 58:31–38CrossRefPubMed

27.

Gnant M, Mlineritsch B, Schippinger W et al (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679–691CrossRefPubMed

28.

Brufsky A, Bundred N, Coleman R et al (2008) Integrated analysis of zoledronic acid for prevention of aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole. Oncologist 13:503–514CrossRefPubMed

Title: A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer
Authors: Mohamed S. Zaghloul
Rimoun Boutrus
Hisham El-Hossieny
Yasser Abdel Kader
Inas El-Attar
Mohamed Nazmy
Publication date: 01-08-2010
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 4/2010
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-010-0074-5

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Abstract

Background

Patients and methods

Results

Conclusions

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