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Combinations of Bisphosphonates and Classical Anticancer Drugs: A Preclinical Perspective

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Prevention of Bone Metastases

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 192))

Abstract

Bone metastases are frequent complications in advanced breast and prostate cancer among others, resulting in increased risk of fractures, pain, hypercalcaemia of malignancy and a reduction in patient independence and mobility. Bisphosphonates (BPs) are in wide clinical use for the treatment of cancer-induced bone disease associated with advanced cancer, due to their potent ability to reduce skeletal-related events (SREs) and improve quality of life. Despite the profound effect on bone health, the majority of clinical studies have failed to demonstrate an overall survival benefit of BP therapy. There is increasing preclinical evidence to suggest that inclusion of the most potent nitrogen-containing BPs (NBPs) in combination therapy results in increased antitumour effects and improved survival, but that the particular schedules used are of key importance to achieve optimal benefit. Recent clinical data have suggested that there may be effects of adjuvant NBP therapy on breast tumours outside the skeleton. These findings have led to renewed interest in the use of BPs in cancer therapy, in particular how they can be included as part of adjuvant protocols. Here we review the key data reported from preclinical model systems investigating the effects of combination therapy including BPs with particular emphasis on breast and prostate cancer.

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Abbreviations

ANZAC:

AdditioN of Zoledronic Acid to neo-adjuvant Combination chemotherapy

AZURE:

Adjuvant Zoledronic acid redUce Recurrence

bFGF:

basic Fibroblast Growth Factor

BP:

BisPhosphonate

DMC:

Dorsal Microcirculation Chamber

EC:

Endothelial Cells

ER:

Estrogren Receptor

FEC:

5-Fluorouracil + Epirubicin + Cyclophosphamide

HER2:

Human Epidermal growth factor Receptor 2

HuDMEC:

Human Dermal Microvascular Endothelial Cells

HUVEC:

Human Umbilical Vein Endothelial Cells

GGOH:

GeranylGeraniol

μCT analysis:

micro-Computed Tomography

NBP:

Nitrogen-containing BisPhosphonate

NSCLC:

Non-Small Cell Lung Cancer

PDGF:

Platelet-Derived Growth Factor

PSA:

Prostate Specific Antigen

SCID:

Severe Combined ImmunoDeficiency

SCLC:

Small Cell Lung Cancer

SRE:

Skeletal Related Event

UFT:

TegaFur-Uracil

VEGF:

Vascular Endothelial Growth Factor

ZANTE:

Zoledronic acid ANd TaxoterE

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Authors and Affiliations

  1. Academic Unit of Clinical Oncology, DU39 Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

    Dr. Maria Michailidou & Dr. Ingunn Holen

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  1. Dr. Maria Michailidou
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  2. Dr. Ingunn Holen
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Correspondence to Ingunn Holen .

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  1. , Dept. of Medical Oncology, Kantonsspital St. Gallen, Rorschacherstr. 95, St. Gallen, 9007, Switzerland

    Markus Joerger

  2. Chirurgische Klinik, Abt. Allgemeine Chirurgie, Universitätsklinikum Wien, Währinger Gürtel 18-20, Wien, 1090, Austria

    Michael Gnant

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Michailidou, M., Holen, I. (2012). Combinations of Bisphosphonates and Classical Anticancer Drugs: A Preclinical Perspective. In: Joerger, M., Gnant, M. (eds) Prevention of Bone Metastases. Recent Results in Cancer Research, vol 192. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21892-7_7

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