Date of Graduation

Summer 8-11-2012

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

James Ferguson, PA-C, MPH

Second Advisor

Annjanette Sommers PA-C, MS

Abstract

Background: The occurrence of skeletal related events (SREs) in patients with solid tumors and multiple myeloma is a concern for both patient and provider due to the subsequent morbidity and risk for further complications. SREs have been defined by researchers as pathological fracture, radiation or surgery to bone, or spinal cord compression. Therapies that prevent SREs are an important supportive measure in the management of cancer patients.

Method: An exhaustive search of available medical literature was performed using the following databases: Medline, CINAHL, and Web of Science. A cited reference search was performed using Web of Science. The keywords used were denosumab, RANK ligand, bisphosphonates, solid tumors, and multiple myeloma.

Results: Three RCTs that met inclusion criteria were analyzed and were relevant for the purposes of this systematic review. Results are as follows: Median time, in months, to first on-study SRE in Fizazi et al, (denosumab: 20.7, zoledronic acid: 17.1; HR, 0.82), Stopeck et al (denosumab: not reached, zoledronic acid: 26.4; HR, 0.82), Henry et al (denosumab: 20.6, zoledronic acid: 16.3; HR, 0.84).

Conclusion: Denosumab has proven to be better than bisphosphonates (particularly zoledronic acid) for the prevention of skeletal related events in patients with solid tumor malignancy or multiple myeloma. Denosumab is easier to administer, can be used without dose adjustment for renal impairment or renal monitoring, and has lower incidence of renal failure and acute phase reactions. Monitoring for hypocalcemia is important, and a supplement should be given as indicated. There is not a significant difference between incidence of osteonecrosis of the jaw (ONJ), or overall survival and disease progression with either denosumab or bisphosphonates.

Keywords: Denosumab, RANK ligand, Bisphosphonates, solid tumors, multiple myeloma

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