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Treatment of bone metastases before the onset of pain

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Abstract

Purpose

Bone metastases are often asymptomatic and are not diagnosed until after the onset of bone pain. However, bone structural integrity may have diminished considerably before pain onset, resulting in increased risk of skeletal-related events. Therefore, we evaluated whether bisphosphonate therapy was differentially beneficial depending on initiation before or after the onset of bone pain.

Methods

Exploratory analyses were performed in patients with bone metastases from breast cancer or lung cancer/other solid tumors enrolled in two randomized trials comparing monthly zoledronic acid versus pamidronate (breast cancer) or placebo (lung cancer/other solid tumors). Analyses included proportion of patients with one or more skeletal-related events, time to first skeletal-related event, and skeletal morbidity rate in patients with and without baseline pain.

Results

Approximately 80 % of patients reported baseline pain. Similar to overall trial results, zoledronic acid reduced the skeletal morbidity rate in all groups. Although some subsets lacked statistical power, benefits were generally greater in patients without baseline pain. For example, in breast cancer, zoledronic acid increased the 25th quartile of time to first skeletal-related event versus pamidronate by 522 days in patients with no baseline pain (median not reached for either group), but by only 10 days in patients with baseline pain. Similar trends were observed in lung cancer.

Conclusions

Benefits from zoledronic acid appeared to be greater if introduced before bone pain onset. Early diagnosis and treatment of bone metastases may delay onset of skeletal-related events.

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Acknowledgments

Funding for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Michael Hobert, PhD, ProEd Communications, Inc.®, for medical editorial assistance with this manuscript.

Conflict of interest

Dr. Costa has received honoraria for lectures at symposia sponsored by Novartis Pharmaceuticals and for participating in advisory board meetings on behalf of Novartis Pharmaceuticals and Amgen. Dr. Lipton has received remuneration for serving on speakers’ bureaus for Novartis Pharmaceuticals and Amgen, has served as a consultant/advisor for Novartis and Amgen, and has received research funding from and provided expert testimony for Novartis. Dr. Hadji has received honoraria, unrestricted educational grants, and research funding from the following companies: Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novartis, Novo Nordisk, Organon, Pfizer, Procter & Gamble, Roche, Sanofi-Aventis, Solvay, and Wyeth. Dr. Chen is an employee of Novartis Pharmaceuticals and owns stock in the company. Dr. Kosmidis has received honoraria for lectures at symposia sponsored by Novartis Pharmaceuticals and for participating in advisory board meetings on behalf of Novartis Pharmaceuticals. Exploratory analyses were supported by Novartis Pharmaceuticals.

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Authors and Affiliations

  1. Hopital de Santa Maria, Serviço de Oncologia, Instituto de Medicina Molecular, Av Professor Egas Moniz, 1649-039, Lisbon, Portugal

    Luis Costa

  2. Penn State Cancer Center, Milton S. Hershey Medical Center, University Drive, Hershey, PA, USA

    Allan Lipton

  3. Philipps-University of Marburg, Universitäts Klinikum Giessen und Marburg, Standort Marburg Baldingerstrasse, Marburg, Germany

    Peyman Hadji

  4. Novartis Oncology, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, USA

    Yin-Miao Chen

  5. 2nd Medical Oncology Department, Hygeia Hospital, Tsoha & Vasilissis Sofias Street, Athens, Greece

    Paris Kosmidis

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  1. Luis Costa
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  2. Allan Lipton
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  3. Peyman Hadji
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  4. Yin-Miao Chen
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  5. Paris Kosmidis
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Correspondence to Luis Costa.

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Costa, L., Lipton, A., Hadji, P. et al. Treatment of bone metastases before the onset of pain. Int J Clin Oncol 18, 531–538 (2013). https://doi.org/10.1007/s10147-012-0414-8

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  • DOI: https://doi.org/10.1007/s10147-012-0414-8

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