title: Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients.
abstract: The proven antiangiogenic activity of zoledronic acid, a third-generation bisphosphonate widely used in bone metastatic cancer patients, led us to investigate if the vascular endothelial growth factor (VEGF)-related zoledronic acid modifications are correlated with survival advantages in advanced breast cancer patients. Forty-two consecutive breast cancer patients with scintigraphic and radiographic evidence of bone metastases were treated with a single infusion of 4 mg zoledronic acid before anticancer chemotherapy. The patients were prospectively evaluated for circulating levels of VEGF and interferon-gamma (IFN-gamma) just before and at 1, 2, 7, and 21 days after zoledronic acid infusion. Afterward, clinical outcome was prospectively monitored. The basal serum VEGF median levels were significantly decreased at each time point, but the major reduction was recorded 21 days after the infusion. In particular, 25 patients of 42 (59.5%) experienced a reduction of at least 25% in the VEGF circulating levels. In contrast, no statistically significant modifications of the IFN-gamma serum levels were recorded. We stratified patients on the basis of this VEGF reduction 21 days after the infusion. No differences in patient features were recorded between those with or without the VEGF reduction. The analysis of survival showed that patients with a reduction in the VEGF circulating levels had a longer time to first skeletal-related event (p = 0.0002), time to bone progression disease (p = 0.0024), and time to performance status worsening (p = 0.0352) than those without the VEGF reduction. No statistically significant differences were recorded in terms of overall survival and time to visceral progression. This study confirms that zoledronic acid could have an in vivo antiangiogenic property and that the VEGF modifications may represent a surrogate marker able to predict time to first skeletal-related event, time to bone progression disease, and time to worsening of performance status.
authors.affiliation: Medical Oncology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giordano
authors.initials: G
authors.lastname: Dicuonzo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Battistoni
authors.forename: Michele
authors.initials: M
authors.lastname: Gavasci
authors.forename: Annalisa
authors.initials: A
authors.lastname: La Cesa
authors.forename: Claudia
authors.initials: C
authors.lastname: Grilli
authors.forename: Vladimir
authors.initials: V
authors.lastname: Virzì
authors.forename: Simona
authors.initials: S
authors.lastname: Gasparro
authors.forename: Laura
authors.initials: L
authors.lastname: Rocci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood / Q000098:blood supply* / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011446:Prospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D042461:Vascular Endothelial Growth Factor A; D000077211:Zoledronic Acid; D007371:Interferon-gamma