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Perspectives in the Elderly Patient: Benefits and Limits of Bisphosphonates and Denosumab

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Prevention of Bone Metastases

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 192))

Abstract

Skeletal metastases affect a large percentage of the cancer population and contribute to a marked decrease in their quality of life and survival, in particular in elderly population. A future end-point of bone-protecting therapy is the demonstration of its ability to prevent or improve results in the treatment of metastatic disease, enlarging their clinical indications in metastatic and osteoporotic setting with different schedules. In this chapter we will discuss on pharmacokinetic and pharmacodynamic interactions of bisphosphonates in elderly, and the preclinical and clinical evidences of anticancer activity of bone-targeted therapies will be critically described. The clinical results of new targeted therapies (such as rank/rankl/OPG inhibition) will be reported both in bone metastatic and in adjuvant settings. Finally, the prevention of cancer treatment-induced bone loss (CTIBL) represents both in young and more in old patients an emerging issue in the bone health care. For this reason, this chapter will discuss the results of current therapies in this clinical setting.

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References

  • Barkin RL, Barkin SJ, Barkin DS (2005) Perception, assessment, treatment, and management of pain in the elderly. Clin Geriatr Med 21(3):465–490

    Article  PubMed  Google Scholar 

  • Coleman RE (1997) Skeletal complications of malignancy. Cancer 80(8 Suppl):1588–1594

    Article  PubMed  CAS  Google Scholar 

  • Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R (2007) Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 110(8):1860–1867

    Article  PubMed  Google Scholar 

  • Saad F (2008) New research findings on zoledronic acid: Survival, pain, and anti-tumour effects. Cancer Treat Rev 34(2):183–192

    Article  PubMed  CAS  Google Scholar 

  • Gridelli C (2007) The use of bisphosphonates in elderly cancer patients. Oncologist 12(1):62–71

    Article  PubMed  CAS  Google Scholar 

  • Addeo R, Nocera V, Faiola V, Vincenzi B, Ferraro G, Montella L, Guarrasi R, Rossi E, Cennamo G, Tonini G, Capasso E, Santini D, Caraglia M, Del Prete S (2008) Management of pain in elderly patients receiving infusion of zoledronic acid for bone metastasis: a single-institution report. Support Care Cancer 16(2):209–214 Epub 2007 Aug 14

    Article  PubMed  Google Scholar 

  • Weide R, Koppler H, Antras L, Smith M, Chang MP, Green J, Wintfeld N, Neary MP, Duh MS (2010) Renal toxicity in patients with multiple myeloma receiving zoledronic acid vs. ibandronate: a retrospective medical records review. J Cancer Res Ther 6(1):31–35

    Article  PubMed  CAS  Google Scholar 

  • Pillai G, Gieschke R, Goggin T, Barrett J, Worth E, Steimer JL (2006) Population pharmacokinetics of ibandronate in Caucasian and Japanese healthy males and postmenopausal females. Int J Clin Pharmacol Ther 44(12):655–667

    PubMed  CAS  Google Scholar 

  • Goldschmidt H, Lannert H, Bommer J, Ho AD (2000) Multiple myeloma and renal failure. Nephrol Dial Transplant 15:301–304

    Article  PubMed  CAS  Google Scholar 

  • Patterson WP, Reams GP (1992) Renal toxicities of chemotherapy. Semin Oncol 19:521–858

    PubMed  CAS  Google Scholar 

  • Tanvetyanon T, Stiff PJ (2006) Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol 17:897–907

    Article  PubMed  CAS  Google Scholar 

  • Body JJ, Coleman R, Clezardin P, Ripamonti C, Rizzoli R, Aapro M (2007) International society of geriatric oncology (SIOG) clinical practice recommendations for the use of bisphosphonates in elderly patients. Eur J Cancer 43:852–858

    Article  PubMed  CAS  Google Scholar 

  • Boonen S, Black DM, ColĂłn-Emeric CS, Eastell R, Magaziner JS, Eriksen EF, Mesenbrink P, Haentjens P, Lyles KW (2010) Efficacy and safety of a once-yearly intravenous zoledronic acid 5 mg for fracture prevention in elderly postmenopausal women with osteoporosis aged 75 and older. J Am Geriatr Soc 58(2):292–299 Epub 2010 Jan 8

    Article  PubMed  Google Scholar 

  • Santini D, Fratto ME, Vincenzi B et al (2006) Zoledronic acid in the management of metastatic bone disease. Expert Opin Biol Ther 6(12):1333–1348

    Article  PubMed  CAS  Google Scholar 

  • ClĂ©zardin P, Ebetino FH, Fournier PGJ (2005) Bisphosphonates and cancer induced bone disease: beyond their antiresorptive activity. Cancer Res 65:4971–4974

    Article  PubMed  Google Scholar 

  • Santini D, Vespasiani Gentilucci U, Vincenzi B et al (2003) The antineoplastic role of bisphosphonates: from basic research to clinical evidence. Ann Oncol 14:1468–1476

    Article  PubMed  CAS  Google Scholar 

  • Santini D, Galluzzo S, Vincenzi B et al (2007) New developments of aminobisphosphonates: the double face of Janus. Ann Oncol 18(Suppl 6):vi164-7

    PubMed  Google Scholar 

  • Caraglia M, Santini D, Marra M et al (2006) Emerging anti-cancer molecular mechanisms of aminobisphosphonates. Endocr Relat Cancer 13:7–26

    Article  PubMed  CAS  Google Scholar 

  • DaubinĂ© F, CĂ©line Le Gall C, Gasser J, Green J, ClĂ©zardin P (2007) Antitumor Effects of Clinical Dosing Regimens of Bisphosphonates in Experimental Breast Cancer Bone Metastasis. JNCI 99(4):322–330

    PubMed  Google Scholar 

  • Diel IJ, Solomayer EF, Costa SD et al (1998) Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 339:357–363

    Article  PubMed  CAS  Google Scholar 

  • Powles T, McCroskey E, Paterson A (2006) Oral bisphosphonates as adjuvant therapy for operable breast cancer. Clin Cancer Res 12:6301s–6304s

    Article  PubMed  CAS  Google Scholar 

  • Saarto T, Vehmanen L, Blomqvist C, Elomaa I (2006) 10-year follow-up of the efficacy of clodronate on bone mineral density (BMD) in early stage breast cancer. J Clin Oncol ASCO Annual Meeting Proceedings Part I 24(18 Suppl):Abstr 676

    Google Scholar 

  • Jaschke A, Bastert G, Solomayer EF et al (2004) Adjuvant clodronate treatment improves the overall survival of primary breast cancer patients with micrometastases to bone marrow—a longtime follow-up. J Clin Oncol (Meeting Abstracts) 22:529

    Google Scholar 

  • Ha TC, Li H (2007) Meta-analysis of clodronate and breast cancer survival. Br J Cancer 6:1796–1801

    Article  Google Scholar 

  • Eidtmann H, Bundred NJ, DeBoer R et al. (2008) The effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36 months follow-up of ZO-FAST. 31st Annual Meeting of the San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, TX (abstr 44)

    Google Scholar 

  • Aapro M (2006) Improving bone health in patients with early breast cancer by adding bisphosphonates to letrozole: The Z-ZO-E-ZOFAST program. Breast 15(Suppl 1):S30–S40

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Eidtmann H, Bundred NJ, DeBoer R et al (2010) The effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36 months follow-up of ZO-FAST. Ann Oncol 21(11):2188–2194

    Article  PubMed  CAS  Google Scholar 

  • Coleman R et al. (2009) Impact of Zoledronic Acid in Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole: Z-FAST, ZO-FAST, and E-ZO-FAST. Presented at: 32nd SABCS; 2009. Abstract 4082

    Google Scholar 

  • Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, RĂĽcklinger E, Greil R, ABCSG-12 Trial Investigators, Marth C (2009b) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360(7):679–691 Erratum in: N Engl J Med. 2009 May 28;360(22):2379

    Article  PubMed  CAS  Google Scholar 

  • Chlebowski RT, Chen Z, Cauley JA, Anderson G, Rodabough RJ, McTiernan A, Lane DS, Manson JE, Snetselaar L, Yasmeen S, O’Sullivan MJ, Safford M, Hendrix SL, Wallace RB (2010) Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 28(22):3582–3590 Epub 2010 Jun 21

    Article  PubMed  CAS  Google Scholar 

  • Rennert G, Pinchev M, Rennert HS (2010) Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 28(22):3577–3581 Epub 2010 Jun 21

    Article  PubMed  CAS  Google Scholar 

  • Coleman RE, Winter MC, Cameron D, Bell R, Dodwell D, Keane MM, Gil M, Ritchie D, Passos-Coelho JL, Wheatley D, Burkinshaw R, Marshall SJ, Thorpe H, AZURE (BIG01/04) Investigators (2010) The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer. Br J Cancer 102(7):1099–1105 Epub 2010 Mar 16

    Article  PubMed  CAS  Google Scholar 

  • Coleman RE, Thorpe HC, Cameron D, Dodwell D, Burkinshaw R, Keane M, Gil M, Houston SJ, Grieve RJ, Barrett-Lee PJ, Ritchie D, Davies C, Bell R[S4-5] Adjuvant Treatment with Zoledronic Acid in Stage II/III Breast Cancer. The AZURE Trial (BIG 01/04). Presented at: SABCS 2010

    Google Scholar 

  • Mauri D, Valachis A, Polyzos NP et al (2010) Does Adjuvant Bisphosphonate in Early Breast Cancer Modify the Natural Course of the Disease? A Meta-Analysis of Randomized Controlled Trials. J Natl Compr Canc Netw 8:279–286

    PubMed  CAS  Google Scholar 

  • Mason MD, Sydes MR, Glaholm J et al (2007) Oral sodium clodronate for nonmetastatic prostate cancer–results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873). J Natl Cancer Inst 99(10):765–776

    Article  PubMed  CAS  Google Scholar 

  • Guise TA (2000) Molecular mechanisms of osteolytic bone metastases. Cancer 88(12 Suppl):2892–2898

    Article  PubMed  CAS  Google Scholar 

  • Stopeck A, Lipton A, Body JJ et al (2010) Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized double-blind study. J Clin Oncol 28(35):5132–5139

    Article  PubMed  CAS  Google Scholar 

  • Vadhan-Raj S, Henry DH, von Moos R et al (2010) Denosumab in the treatment of bone metastases from advanced cancer or multiple myeloma (MM): Analyses from a phase III randomized trial. J Clin Oncol 28(Suppl):15s [abstract 9042]

    Google Scholar 

  • Fizazi K, Carducci MA, Smith MR et al (2010) A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer. J Clin Oncol 28(Suppl):18s [abstract LBA4507]

    Google Scholar 

  • Cummings SR, San Martin J, McClung MR et al (2009) FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  PubMed  CAS  Google Scholar 

  • Ellis GK, Bone HG, Chlebowski R et al (2009) Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res Treat 118:81–87

    Article  PubMed  CAS  Google Scholar 

  • National Institutes of Health. A randomised, double-blind, placebo-controlled, multi-centre phase 3 study to determine the treatment effect of denosumab in subjects with non-metastatic breast cancer receiving aromatase inhibitor therapy. Clinicaltrials.gov web site. Available at: http://clinicaltrials.gov/ct2/show/NCT00556374. Accessed August 6, 2010

  • Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C, Denosumab HALT Prostate Cancer Study Group (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361(8):745–755 Epub 2009 Aug 11

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology, University Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Rome, Italy

    Daniele Santini & Maria Elisabetta Fratto

  2. Institut Multidisciplinaire d’Oncologie, IMO Clinique de Genolier, Genolier, Switzerland

    Matti Aapro

Authors
  1. Daniele Santini
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  2. Maria Elisabetta Fratto
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  3. Matti Aapro
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Corresponding author

Correspondence to Daniele Santini .

Editor information

Editors and Affiliations

  1. , Dept. of Medical Oncology, Kantonsspital St. Gallen, Rorschacherstr. 95, St. Gallen, 9007, Switzerland

    Markus Joerger

  2. Chirurgische Klinik, Abt. Allgemeine Chirurgie, Universitätsklinikum Wien, Währinger Gürtel 18-20, Wien, 1090, Austria

    Michael Gnant

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Santini, D., Fratto, M.E., Aapro, M. (2012). Perspectives in the Elderly Patient: Benefits and Limits of Bisphosphonates and Denosumab. In: Joerger, M., Gnant, M. (eds) Prevention of Bone Metastases. Recent Results in Cancer Research, vol 192. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21892-7_8

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  • DOI: https://doi.org/10.1007/978-3-642-21892-7_8

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-21891-0

  • Online ISBN: 978-3-642-21892-7

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