drugset / Trial / NCT00525759
Investigating the Biological Effects of the Addition of Zoledronic Acid to Pre-operative Chemotherapy in Breast Cancer
Phase 2
Completed
40 enrolled
Sheffield Teaching Hospitals NHS Foundation Trust
University of Sheffield · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
There is clear preclinical in vitro and in vivo evidence of sequence dependent synergy between chemotherapy agents and zoledronic acid. The aim of the study is to investigate if the synergistic increase in tumour cell apoptosis observed in preclinical studies occurs in patients. The hypothesis for this study is that there may be anti-tumour benefits of the sequential application of chemotherapy agents followed by zoledronic acid in patients with invasive breast cancer.
Timeline
- Start
- 2007-07
- Primary completion
- 2010-01
- Completion
- 2010-01
Publications
- Background Jagdev SP, Coleman RE, Shipman CM, Rostami-H A, Croucher PI. The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer. 2001 Apr 20;84(8):1126-34. doi: 10.1054/bjoc.2001.1727.
- Background Neville-Webbe HL, Rostami-Hodjegan A, Evans CA, Coleman RE, Holen I. Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer. 2005 Jan 20;113(3):364-71. doi: 10.1002/ijc.20602.
- Background Ottewell PD, Jones M, Coleman RE, Holen I. Synergistic effects of cytotoxic drugs and anti-resorptive agents in vitro and in vivo. In 29th Annual San Antonio Breast Cancer Symposium Vol.100 Suppl.1 Abstract 6102, Breast Cancer Research and Treatment
- Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
- Winter MC, Wilson C, Syddall SP, Cross SS, Evans A, Ingram CE, Jolley IJ, Hatton MQ, Freeman JV, Mori S, Holen I, Coleman RE. Neoadjuvant chemotherapy with or without zoledronic acid in early breast cancer--a randomized biomarker pilot study. Clin Cancer Res. 2013 May 15;19(10):2755-65. doi: 10.1158/1078-0432.CCR-12-3235. Epub 2013 Mar 20.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Zoledronic acid | Other / unclassified | 4 mg | Intravenous |
| Comparator | Cyclophosphamide | Other / unclassified | 500 mg/m2 | Intravenous |
| Comparator | Docetaxel | Small molecule | 100 mg/m2 | Intravenous |
| Comparator | Epirubicin | Small molecule | 100 mg/m2 | Intravenous |
| Comparator | fluorouracil | Small molecule | 500 mg/m2 | Intravenous |