Address of Corresponding Author

Oncology 2006;70:147-153 (DOI: 10.1159/000093006)

  Key Words

• Zoledronic acid
• Synergy
• Fluvastatin
• Gemcitabine

  Abstract

Objectives: To identify synergistic combinations of clinically available agents with zoledronic acid which would enhance antitumor activity as measured by median effect isobologram analysis and apoptosis assays in vitro. Methods: The interaction of zoledronic acid as a doublet with either carboplatin, cisplatin, 5'DFUR, docetaxel, epirubicin, fluvastatin, gemcitabine, imatinib, paclitaxel, trastuzumab, or vinorelbine was studied in a 72-hour in vitro system using defined human cancer cell lines grown as a monolayer in exponential phase. Drug effect on growth was measured by a standard MTT assay. Median effect isobologram analysis was applied to the results to determine the presence of synergism, additive effects, or antagonism of drug combinations. Synergistic combinations were also assayed by a cytoplasmic histone-associated DNA fragmentation apoptosis assay to verify that the effect was not cytostatic. Results: Zoledronic acid with gemcitabine demonstrated global cytotoxic synergy across 7 of 8 cell lines. Clinically achievable concentrations of fluvastatin with zoledronic acid also demonstrated synergy in 7 of 8 cell lines. All the breast cancer cell lines were sensitive. Zoledronic acid and epirubicin were antagonistic in all 4 breast cell lines studied. Conclusions: Combinations of zoledronic acid with either gemcitabine or fluvastatin may have a therapeutic role in treatment of bone metastasis of selected malignancies.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Dr. D.R. Budman
Don Monti Division of Oncology, North Shore University Hospital
New York University, 300 Community Drive
Manhasset, NY 11030 (USA)
Tel. +1 516 562 8958, Fax +1 516 562 8950, E-Mail budman@nshs.edu

  Article Information

Received: August 31, 2005
Accepted after revision: February 25, 2006
Published online: April 26, 2006
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 2, Number of References : 41