title: Changes in bone resorption and vascular endothelial growth factor after a single zoledronic acid infusion in cancer patients with bone metastases from solid tumours.
abstract: Zoledronic acid (Zometa, ZOL) is increasingly used to treat tumour-induced bone disease, and is also reported to have antiangiogenic properties in vivo. In this study, we have investigated the correlations between changes in the proangiogenic cytokine, vascular endothelial growth factor (VEGF), and markers of bone resorption in a cohort of patients with metastatic bone disease, following a single infusion of ZOL. Twenty-four consecutive selected cancer patients with scintigraphic and radiographic evidence of bone metastases were treated for the first time with a single infusion of 4 mg ZOL. Patients were considered ineligible if they had received any steroid therapy, radiotherapy, chemotherapy, immunotherapy or haemopoietic growth factors in the 4 weeks before or during the study period. Circulating levels of VEGF and beta crosslinked type I collagen C-telopeptide (betaCTX) were measured at base-line and at 1, 2, 7 and 21 days following ZOL infusion. The majority of our patients (23/24) developed a significant reduction in circulating levels of betaCTX at just 1 day after the single zoledronic acid infusion, median percentage decrease 67.05% (95% CI, 52.39%; 76.27%). This reduction persisted at all following time points in almost all subjects in our patient population (day 2, 95.8%; day 7, 100%; day 21, 91.7%). The median decrease at day 2 was 85.67% (95% CI, 78.23%; 90.16%); at day 7, 67.38% (95% CI, 67.38%; 86.98); and at day 21, 76.89% (95% CI, 35.00%; 83.16%). Moreover, a linear regression model with variance analysis demonstrated a statistically significant correlation between median VEGF and betaCTX circulating levels at each of the time points (1, 2, 7 and 21 days after ZOL infusion). The present work demonstrates that a single infusion of ZOL was able to induce a rapid and long lasting decrease of betaCTX plasma levels in the majority (23/24) of the included cancer patients. Furthermore, we found that there is a correlation between the levels of VEGF and betaCTX following ZOL treatment. Future clinical trials should be designed to prospectively evaluate the prognostic role of reduction of betaCTX and VEGF in response to ZOL to predict clinical and skeletal outcome.
authors.affiliation: Clinical Oncology, University Campus Bio-Medico, 00155 Rome, Italy. d.santini@unicampus.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Hannon
authors.forename: Janet E
authors.initials: JE
authors.lastname: Brown
authors.forename: Giordano
authors.initials: G
authors.lastname: Dicuonzo
authors.forename: Silvia
authors.initials: S
authors.lastname: Angeletti
authors.forename: Annalisa
authors.initials: A
authors.lastname: La Cesa
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.forename: Alfredo
authors.initials: A
authors.lastname: Budillon
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Ingunn
authors.initials: I
authors.lastname: Holen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000097:blood / Q000556:secondary; D001862:Bone Resorption; D024042:Collagen Type I / Q000378:metabolism*; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D000077211:Zoledronic Acid
chemical_list: D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid