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. 2012 Nov 21;1(3):74-80.
doi: 10.1016/j.jbo.2012.10.001. eCollection 2012 Dec.

Skeletal morbidity rates over time in patients with bone metastases from solid tumors reported in bone modifying agents randomised trials

Michael Poon  1 , Liang Zeng  1 , Liying Zhang  1 , Marko Popovic  1 , Ronald Chow  1 , Henry Lam  1 , Gillian Bedard  1 , Urban Emmenegger  1 , Christine Simmons  2 , Edward Chow  1
Affiliations

Skeletal morbidity rates over time in patients with bone metastases from solid tumors reported in bone modifying agents randomised trials

Michael Poon et al. J Bone Oncol. .

Abstract

Objective: Skeletal related events (SREs) are common in patients with bone metastases and lead to decreased quality of life and functional status. The definition of an SRE has evolved over the years and now excludes hypercalcemia of malignancy due to its low incidence. The purpose of this review was to investigate if advances in bone-targeted therapies have decreased skeletal morbidity rates (SMR) over time.

Methods: A literature search was conducted in several databases to identify phase III results from bone-targeted therapy trials from 1980 through September 2011. Graphs were created to document the trends of the natural log of SMR over the mean time of enrolment for all placebo and intervention arms. Statistical hypothesis testing was employed to account for confounding factors.

Results: A total of 14 studies were identified which reported the SMR from phase III trials from 1990 to 2007. A statistically significant downward trend was observed in the placebo arms of trials over time; a similar trend was seen in all intervention arms. In a direct comparison of intervention against placebo arms, it was found that there was a significant decreasing time trend (p<0.0001) and a significant departure in SMR from placebo to intervention arms (p=0.0348). These results were seen even after accounting for the confounding factors of histology and differences in drugs.

Conclusion: The decrease in SMR over time may not only be a result of advancements with bone targeted agents, but also due to better management and awareness of events associated with bone metastases.

Keywords: Bisphosphonates; Bone metastases; Skeletal morbidity rates time trend; Skeletal related events.

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Figures

Fig. 1
Fig. 1
Skeletal morbidity rates (SMR) over time of placebo arms in phase III trials with weighted linear regression model.
Fig. 2
Fig. 2
SMR rates over time of all intervention arms in phase III trials with weighted linear regression model.
Fig. 3
Fig. 3
SMR rates over time of zoledronic acid treatment arms in phase III trials with weighted linear regression model.
Fig. 4
Fig. 4
Comparison of SMR trends for all intervention arms (solid circle) against all placebo arms (open triangle).
See this image and copyright information in PMC

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References

    1. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clinical Cancer Research. 2006;12(20):6243s–6249s. - PubMed
    1. Saad F, Chen YM, Gleason DM, Chin J. Continuing benefit of zoledronic acid in preventing skeletal complications in patients with bone metastases. Clinical Genitourinary Cancer. 2007;5(6):390–396. - PubMed
    1. Theriault RL, Lipton A, Hortobagyi GN, Leff R, Gluck S, Stewart JF. Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 aredia breast cancer study group. Journal of Clinical Oncology. 1999;17(3):846–854. - PubMed
    1. Lipton A, Theriault RL, Hortobagyi GN, Simeone J, Knight RD, Mellars K. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88(5):1082–1090. - PubMed
    1. Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. British Journal of Cancer. 1987;55(1):61–66. - PMC - PubMed

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