Skip to main content
SpringerLink
Log in

Bisphosphonates: Prevention of Bone Metastases in Lung Cancer

  • Chapter
  • First Online:
Prevention of Bone Metastases

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

Abstract

In patients with lung cancer, bone is one of the most frequent sites of distant spread, with approximately 30% of patients developing skeletal metastases. About half of these patients will experience a skeletal-related event, the occurrence of which not only affects quality of life, but is also associated with poor prognosis. Bisphosphonates are currently the mainstay for treating bone metastases in patients with lung cancer, with proven beneficial effects on prevention and delay of skeletal complications. Their role in preventing the development of skeletal metastases, their anti-tumoral properties and their effect on survival remain to be elucidated. Other bone-targeted therapies are being investigated in phase II and III clinical trials and might expand the therapeutic arsenal in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AUC:

Area under the curve

BALP:

Bone-specific alkaline phosphatase

CT:

Computed tomography (scan)

FDG-PET:

Fluorine-18 deoxyglucose positron emission tomography

Gy:

Gray

HR:

Hazard ratio

IV:

Intravenous

MRI:

Magnetic resonance imaging

PD:

Progressive disease

QOL:

Quality of life

NSCLC:

Non-small cell lung cancer

NTX:

N-telopeptide of type I collagen

ONJ:

Osteonecrosis of the jaw

RANKL:

Receptor activator of nuclear factor kappa B ligand

RR:

Relative risk

SCLC:

Small cell lung cancer

SRE:

Skeletal-related event

References

  • Berger W, Kubista B, Elbling L et al (2005) The N-containing bisphosphonate zoledronic acid exerts potent anticancer activity against non-small cell lung cancer cells by inhibition of protein geranylgeranylation. Proc Am Assoc Cancer Res 46: Abstr 4981

    Google Scholar 

  • Bezjak A (2003) Palliative therapy for lung cancer. Semin Surg Oncol 21:138–147

    Article  PubMed  Google Scholar 

  • Brown JE, Cook RJ, Major P (2005) Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer and other solid tumors. J Natl Cancer Inst 97:59–69

    Article  PubMed  CAS  Google Scholar 

  • Budman DR, Calabro A (2006) Zoledronic acid (Zometa®) enhances the cytotoxic effect of gemcitabine and fluvastatin: in vitro isobologram studies with conventional and nonconventional cytotoxic agents. Oncology 70:147–153

    Article  PubMed  CAS  Google Scholar 

  • Bury T, Barreto A, Daenen F et al (1998) Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer. Eur J Nucl Med 25:1244–1247

    Article  PubMed  CAS  Google Scholar 

  • Chow E, Harris K, Fan G et al (2007) Meta-analysis of palliative radiotherapy trials for bone metastases. Clin Oncol 19:S26

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • D’Addario G, Felip E (2008) Non-small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 19 (Suppl 1):ii39–ii40

    Google Scholar 

  • Delea T, Langer C, McKiernan J et al (2004) The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer. Oncology 67:390–396

    Article  PubMed  Google Scholar 

  • Delea TE, McKiernan J, Brandman J et al (2006) Impact of skeletal complications on total medical care costs among patients with bone metastases of lung cancer. J Thorac Oncol 1:571–576

    Article  PubMed  Google Scholar 

  • de Marinis F, Eberhardt W, Harper PG et al (2009) Bisphosphonate use in patients with lung cancer and bone metastases. Recommendations of a European expert panel. J Thorac Oncol 4(10):1280–1288

    Article  PubMed  Google Scholar 

  • Fizazi K, Lipton A, Mariete X et al (2009) Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer or other neoplasms after intravenous bisphosphonates. J Clin Oncol 27:1534–1546

    Article  Google Scholar 

  • Henry D, von Moos R, Vadhan-Ray S et al (2009) A double-blind, randomized study of denosumab versus zoledronic acid for the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. Eur J Cancer 7(suppl):11

    Google Scholar 

  • Hetzel M, Arslandemir C, König HH et al (2003) F-18NaF PET for detection of bone metastases in lung cancer: accuracy, cost-effectiveness, and impact on patient management. J Bone Miner Res 18(12):2206–2214

    Article  PubMed  Google Scholar 

  • Hirsh V, Major PP, Lipton A et al (2008) Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity. J Thorac Oncol 3:228–236

    Article  PubMed  Google Scholar 

  • Iordanidou L, Trivizaki E, Saranti S et al (2006) Is there a role of whole body bone scan in early stages of non small cell lung cancer patients. J BUON 11:491–497

    PubMed  CAS  Google Scholar 

  • Johnson FM, Tang X, Tran H et al (2009) Phase II study of dasatinib in non-small cell lung cancer (NSCLC). J Clin Oncol 27(Suppl 15):e19015

    Google Scholar 

  • Karamanos N, Zarogoulidis K, Boutsikou E et al (2010) Prolonged survival and time to disease progression with zoledronic acid in patients with bone metastases from non-small cell lung cancer. J Clin Oncol 28(15):e18077

    Google Scholar 

  • Kasalicky J, Krajska V (1998) The effect of repeated strontium-89 chloride therapy on bone palliation in patients with skeletal cancer metastases. Eur J Nuc Med 25:1362–1367

    Article  CAS  Google Scholar 

  • Kawatani M, Osada H (2009) Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases. Cancer Sci 100:1999–2005

    Article  PubMed  CAS  Google Scholar 

  • Kosteva J, Langer CJ (2004) Incidence and distribution of skeletal metastases in NSCLC in the era of PET. Lung Cancer 46(1):S45

    Google Scholar 

  • Kosteva J, Langer C (2008) The changing landscape of the medical management of skeletal metastases in non small cell lung cancer. Curr Opin Oncol 20:155–161

    Article  PubMed  CAS  Google Scholar 

  • Langer C, Hirsh V (2010) Skeletal morbidity in lung cancer patients with bone metastases: demonstrating the need for early diagnosis and treatment with bisphosphonates. Lung Cancer 67:4–11

    Article  PubMed  Google Scholar 

  • Lipton A, Steger GG, Figueroa J et al (2007) Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 25:4431–4437

    Article  PubMed  CAS  Google Scholar 

  • Lipton A, Cook R, Saad F et al (2008) Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer 113(1):193–201

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto S, Kimura S, Segawa H et al (2005) Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines. Lung Cancer 47:31–37

    Article  PubMed  Google Scholar 

  • McQuay HJ, Collins SL, Carroll D et al (2000) Radiotherapy for the palliation of painful bone metastases. Cochrane Database Syst Rev CD001793

    Google Scholar 

  • Pfister DG, Johnson DH, Azzoli CG et al (2004) American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 22(2):330–353

    Article  PubMed  Google Scholar 

  • Ripamonti CI, Maniezzo M, Campa T et al (2009) Decreased occurrence of osteonecrosis of the jaw after implementation of preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 20:137–145

    Article  PubMed  CAS  Google Scholar 

  • 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. Cancer 100(12):2613–2621

    Article  PubMed  CAS  Google Scholar 

  • Schirrmeister H, Arslandemir C, Glatting G et al (2004) Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 31:964–968

    Article  PubMed  Google Scholar 

  • Spizzo G, Seeber A, Mitterer M (2009) Routine use of pamidronate in NSCLC with bone metastasis: results from a retrospective analysis. Anticancer Res 29(12):5245–5249

    PubMed  CAS  Google Scholar 

  • Stephens J, Kaura S, Botteman MF (2009) Cost-effectiveness of zoledronic acid versus placebo in the management of skeletal metastases in lung cancer patients (LC pts): Comparison across three European countries. J Clin Oncol 27(15S):8081

    Google Scholar 

  • Takenaka D, Ohno Y, Matsumoto K et al (2008) Detection of bone metastases in non-small cell lung cancer patients: comparison of whole-body diffusion-weighted imaging (DWI), whole-body MRI imaging without and with DWI, whole-body FDG-PET/CT, and bone scintigraphy. J Magn Reson Imaging 30:298–308

    Article  Google Scholar 

  • Tsuya A, Kurata T, Tamura K (2007) Skeletal metastases in non-small cell lung cancer: a retrospective study. Lung Cancer 57:229–232

    Article  PubMed  Google Scholar 

  • US National Institutes of Health (2011a). A study to evaluate the safety and efficacy of zoledronic acid in the prevention or delaying of bone metastasis in patients with stage IIIA and IIIB non-small cell lung cancer. Available at: http://clinicaltrials.gov/ct2/show/NCT00172042?term=zoledronic+acid+AND+lung+cancer&rank=1

  • US National Institutes of Health (2011b). Non-small cell lung cancer study US75(Z-PACT). Available at: http://clinicaltrials.gov/ct2/show/NCT00086268?term=zoledronic+acid+AND+lung+cancer&rank=9

  • 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 17:986–989

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pulmonology, Respiratory Oncology, University Hospital Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium

    Lynn Decoster & Kristiaan Nackaerts

  2. Department of Lung Diseases, San Camillo High Specialization Hospital, Rome, Italy

    Filippo de Marinis

  3. Oncology Unit, Sotiria General Hospital, Athens, Greece

    Kostas Syrigos

  4. Department of Medicine and Oncology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada

    Vera Hirsh

Authors
  1. Lynn Decoster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Filippo de Marinis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kostas Syrigos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vera Hirsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kristiaan Nackaerts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristiaan Nackaerts .

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

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Decoster, L., de Marinis, F., Syrigos, K., Hirsh, V., Nackaerts, K. (2012). Bisphosphonates: Prevention of Bone Metastases in Lung Cancer. 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_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-21892-7_4

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-21891-0

  • Online ISBN: 978-3-642-21892-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation