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Subcutaneous Bortezomib

In Multiple Myeloma

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Abstract

A subcutaneous formulation of bortezomib is now indicated in the EU and the US for the treatment of patients with multiple myeloma. This article reviews pharmacological, therapeutic efficacy and tolerability data relevant to the utilization of subcutaneous bortezomib (Velcade®) in the treatment of patients with multiple myeloma. In a randomized, nonblind, phase III study, subcutaneous bortezomib was noninferior to intravenous bortezomib in the treatment of adults with relapsed multiple myeloma, as determined by the overall response rate after four cycles of therapy (primary endpoint). No significant differences between the subcutaneous and intravenous bortezomib formulations were observed in the median time to first response, median progression-free survival, median time to progression and 1-year overall survival. Compared with intravenous bortezomib, subcutaneous bortezomib confers a significant advantage with respect to the incidence of peripheral neuropathy (all grades, grade ≥2 and grade ≥3). As a consequence, it provides a new treatment option for patients with multiple myeloma, particularly those with pre-existing neuropathy or at a high risk of developing peripheral neuropathy.

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References

  1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60.

    Article  PubMed  CAS  Google Scholar 

  2. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: multiple myeloma. 1.2013 [online]. http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed 26 Nov 2012.

  3. Mateos M-V. Subcutaneous bortezomib: a step towards optimised drug use. Lancet Oncol. 2011;12(5):410–1.

    Article  PubMed  Google Scholar 

  4. Curran MP, McKeage K. Bortezomib: a review of its use in patients with multiple myeloma. Drugs. 2009;69(7):859–88.

    Article  PubMed  CAS  Google Scholar 

  5. Janssen-Cilag International NV. Velcade 1 mg powder for solution for injection: summary of product characteristics. 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000539/WC500048471.pdf. Accessed 2 Nov 2012.

  6. Millennium Pharmaceuticals Inc. Velcade® (bortezomib) for injection: US prescribing information. 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021602s027lbl.pdf. Accessed 14 Nov 2012.

  7. Boccadoro M, Morgan G, Cavenagh J. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005;5(1):18.

    Article  PubMed  Google Scholar 

  8. Hideshima T, Richardson PG, Anderson KC. Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. Mol Cancer Ther. 2011;10(11):2034–42.

    Article  PubMed  CAS  Google Scholar 

  9. Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012;120(5):947–59.

    Article  PubMed  CAS  Google Scholar 

  10. Wright JJ. Combination therapy of bortezomib with novel targeted agents: an emerging treatment strategy. Clin Cancer Res. 2010;16(16):4094–104.

    Article  PubMed  CAS  Google Scholar 

  11. Zangari M, Terpos E, Zhan F, et al. Impact of bortezomib on bone health in myeloma: a review of current evidence. Cancer Treat Rev. 2012;38(8):968–80.

    Article  PubMed  CAS  Google Scholar 

  12. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study.[published erratum appears in Lancet Oncol. 2011 Jun; 12(6):522]. Lancet Oncol. 2011;12(5):431–40.

    Article  PubMed  Google Scholar 

  13. Moreau P, Karamanesht II, Domnikova N, et al. Pharmacokinetic, pharmacodynamic and covariate analysis of subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma. Clin Pharmacokinet. 2012;51(12):823–9.

    Article  PubMed  CAS  Google Scholar 

  14. Arnulf B, Pylypenko H, Grosicki S, et al. Updated survival analysis of a randomized, phase 3 study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica. 2012;97(12):1925–8.

    Article  PubMed  Google Scholar 

  15. Millennium Pharmaceuticals Inc. A study of subcutaneous and intravenous Velcade in patients with previously treated multiple myeloma [ClinicalTrials.gov identifier NCT00722566]. US National Institutes of Health, ClinicalTrials.gov [online].http://clinicaltrials.gov. Accessed 26 Nov 2012.

  16. Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102(5):1115–23.

    Article  PubMed  Google Scholar 

  17. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348(26):2609–17.

    Article  PubMed  CAS  Google Scholar 

  18. Durie BG, Harousseau J-L, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467–73.

    Article  PubMed  CAS  Google Scholar 

  19. Delforge M, Bladé J, Dimopoulos MA, et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol. 2010;11(11):1086–95.

    Article  PubMed  CAS  Google Scholar 

  20. Richardson PG, Sonneveld P, Schuster MW, et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol. 2009;144(6):895–903.

    Article  PubMed  CAS  Google Scholar 

  21. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature [published erratum appears in Blood. 2009;113(18):4478]. Blood. 2008;112(5):1593–9.

    Article  PubMed  CAS  Google Scholar 

  22. Palumbo A, Bringhen S, Rossi D, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010;28(34):5101–9.

    Article  PubMed  CAS  Google Scholar 

  23. Mateos M-V, Oriol A, Martínez-López J, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010;11(10):934–41.

    Article  PubMed  CAS  Google Scholar 

  24. Ostendorf W. Administration of parenteral medication. In: Perry A, Potter P, Elkin MK, editors. Nursing interventions & clinical skills. 5th ed. St Louis: Elsevier Mosby; 2012. p. 541–83.

    Google Scholar 

  25. Fundamentals of administration. In: Polovitch M, Whitford J, Olsen M, editors. Chemotherapy and biotherapy guidelines and recommendations for practice. 3rd ed. Pittsburgh: Oncology Nursing Society; 2009. p. 73–104.

  26. Berenson JR, Hillner BE, Kyle RA, et al. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol. 2002;20(17):3719–36.

    Article  PubMed  Google Scholar 

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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  1. Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Sheridan M. Hoy

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  1. Sheridan M. Hoy
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Correspondence to Sheridan M. Hoy.

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The manuscript was reviewed by: M. Delforge, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium; M-V. Mateos, Haematology Department, University Hospital of Salamanca, Salamanca, Spain; P. Moreau, University Hospital, Nantes Cedex 1, France; P.G. Richardson, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

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Hoy, S.M. Subcutaneous Bortezomib. Drugs 73, 45–54 (2013). https://doi.org/10.1007/s40265-013-0006-6

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