Skip to main content

Advertisement

SpringerLink
Log in

The effects of denosumab on calcium profiles in advanced cancer patients with bone metastases

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Objective

To retrospectively examine the incidence and management of hypocalcemia for patients with bone metastases treated with denosumab.

Methods

Patients who had a record of filling a prescription of denosumab for treatment of bone metastases at the outpatient pharmacy at the Odette Cancer Centre from May 2011 to February 2013 were included in the analysis. Demographic information, previous bisphosphonate usage, calcium and albumin values, and adverse events were obtained using the Sunnybrook Electronic Patient Record system (EPR) and the Oncology Symptom Control and Information Resource (OSCIR). Hypocalcemia was defined as a calcium value below 2.0 mmol/L within a 28-day ± 7-day window after the last injection of denosumab based on the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 hypocalcemia.

Results

A total of 55 patients had record of a prescription for denosumab filled with an average age of 62 years (range 40 to 93 years), 18 (32.7 %) were males and 37 (67.3 %) were females. Twenty-nine (52.7 %) patients had primary breast cancer, 12 (21.8 %) prostate, 10 (18.2 %) lung, and 4 (7.3 %) with other types. Using CTCAE grading of hypocalcemia, 17 (32.7 %) patients experienced grade 1, 4 (7.7 %) patients grade 2, 4 (7.7 %) patients grade 3, and 1 (1.9 %) patient grade 4. The number of injections before the incident of hypocalcemia was a median of one injection (range 1 to 14). Time from the first hypocalcemia lab value to normocalcemia was a median of 33 days.

Conclusions

This study found that 9 of 52 (17.3 %) patients had at least one incidence of hypocalcemia of grade 2 or higher after receiving denosumab. Cautionary measures should be taken to avoid hypocalcemia in patients receiving denosumab.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  2. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005

    Article  PubMed Central  PubMed  Google Scholar 

  3. Hird A, Zhang L, Holt T, Fairchild A, DeAngelis C, Loblaw A et al (2009) Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for symptomatic bone metastases: a phase II study. Clin Oncol (R Coll Radiol) 21(4):329–335

    Article  CAS  Google Scholar 

  4. Ford JA, Jones R, Elders A, Mulatero C, Royle P, Sharma P et al (2013) Denosumab for treatment of bone metastases secondary to solid tumours: systematic review and network meta-analysis. Eur J Cancer 49(2):416–430

    Article  CAS  PubMed  Google Scholar 

  5. Peddi P, Lopez-Olivo MA, Pratt GF, Suarez-Almazor ME (2013) Denosumab in patients with cancer and skeletal metastases: a systematic review and meta-analysis. Cancer Treat Rev 39(1):97–104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. XGEVA product monograph (2013) Amgen Canada Inc., Mississauga

  7. Skugor M (2009) Hypocalcemia. The Cleveland Clinic Foundation. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypocalcemia/. Accessed 1 Dec 2013

  8. Health Canada. Notice of Compliance Database (2012) Retrieved from http://www.hc-sc.gc.ca/dhp-mps/prodpharma/notices-avis/noc-acc/index-eng.php

  9. Anonymous (1977) Correcting the calcium. Br Med 1:598

    Google Scholar 

  10. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (2010) National Cancer Institute

  11. Ungprasert P, Cheungpasitporn W, Srivali N, Kittanamongkolchai W, Bischof EF (2013) Life-threatening hypocalcemia associated with denosumab in a patient with moderate renal insufficiency. Am J Emerg Med 31(4):756

    Article  PubMed  Google Scholar 

  12. Milat F, Goh S, Gani LU, Suriadi C, Gillespie MT, Fuller PJ, Teede HJ, Strickland AH, Allan CA (2013) Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer. Bone 55(2):305–308

    Article  CAS  PubMed  Google Scholar 

  13. Body JJ, Lipton A, Henry DH, Stopeck A, Fizazi K, Bone HG, Saad F, Van Poznak CH, De Boer RH et al (2013) Hypocalcemia in patients with metastatic bone disease receiving denosumab. J Clin Oncol (Meeting Abstracts) 31(15), suppl 9628

    Google Scholar 

  14. Autio KA, Farooki A, Glezerman I, Chan A, Barr HC, Seyboth BM, Schneider CW, Heller G, Scher HI, Morris MJ (2013) Risk assessment for severe hypocalcemia requiring hospitalization with denosumab. J Clin Oncol (suppl 6; abstr 115)

  15. Berruti A, Dogliotti L, Bitossi R, Fasolis G, Gorzegno G, Bellina M, Torta M, Porpiglia F, Fontana D, Angeli A (2000) Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline. J Urol 164(4):1248–1253

    Article  CAS  PubMed  Google Scholar 

  16. Murray RM, Grill V, Crinis N, Ho PW, Davison J, Pitt P (2001) Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab 86(9):4133–4138

    Article  CAS  PubMed  Google Scholar 

  17. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377(9768):813–822

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, Richardson GE, Siena S, Maroto P, Clemens M, Bilynskyy B, Charu V, Beuzeboc P, Rader M, Viniegra M, Saad F, Ke C, Braun A, Jun S (2012) Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 48(16):3082–3092

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the generous support of Bratty Family Fund, Michael and Karyn Goldstein Cancer Research Fund, Joseph and Silvana Melara Cancer Research Fund, and Ofelia Cancer Research Fund.

Conflicts of interest

Dr U. Emmenegger has served as a consultant/advisory board member for Amgen.

Author information

Authors and Affiliations

  1. Rapid Response Radiotherapy Program, Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5

    Breanne Lechner, Natalie Pulenzas, Parker Sheehan, May Tsao, Gillian Bedard & Edward Chow

  2. Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Canada

    Carlo DeAngelis, Noreen Jamal & Angie Giotis

  3. Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Canada

    Urban Emmenegger

Authors
  1. Breanne Lechner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlo DeAngelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noreen Jamal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Urban Emmenegger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Natalie Pulenzas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angie Giotis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Parker Sheehan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. May Tsao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gillian Bedard
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Edward Chow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edward Chow.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lechner, B., DeAngelis, C., Jamal, N. et al. The effects of denosumab on calcium profiles in advanced cancer patients with bone metastases. Support Care Cancer 22, 1765–1771 (2014). https://doi.org/10.1007/s00520-014-2142-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-014-2142-2

Keywords

Search

Navigation