Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients.
OBJECTIVE
The commercial availability of zoledronic acid, a third generation bisphosphonate, prompted us to evaluate the modifications in angiogenic cytokines levels after a single i.v. infusion of this drug.


METHODS
Thirty consecutive cancer patients with scintigraphic and radiographic evidence of bone metastases were treated with a single infusion of 4 mg of zoledronic acid before any chemotherapy. The patients were prospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) just before and at 1, 2, 7, and 21 days after zoledronic acid infusion.


RESULTS
Basal serum VEGF median levels were significantly decreased at days 2 (-23%), 7 (-28%), and 21 (-34%) after zoledronic acid infusion (P = 0.0498, 0.0090, and 0.0011, respectively). Serum PDGF levels were significantly decreased by 25% 1 day after zoledronic acid infusion (P = 0.0032). This effect on circulating PDGF levels persisted for 2 days after bisphosphonate infusion (P = 0.0050). PDGF levels had returned to values similar to the median basal value at 7 and 21 days. Moreover, a linear regression model with variance analysis showed a significant positive correlation between basal VEGF and PDGF values but not at the following time points. No significant differences were recorded in platelet levels, WBC count, or hemoglobin concentration before and after zoledronic acid single infusion.


CONCLUSIONS
This study confirms that zoledronic acid could have an in vivo antiangiogenic property through a significant and long-lasting reduction in serum VEGF levels.
Santini
Daniele
D
Medical Oncology, Department of Laboratory Medicine, Campus Bio-Medico University, 00155 Rome, Italy.
Vincenzi
Bruno
B
Dicuonzo
Giordano
G
Avvisati
Giuseppe
G
Massacesi
Cristian
C
Battistoni
Fabrizio
F
Gavasci
Michele
M
Rocci
Laura
L
Tirindelli
Maria Cristina
MC
Altomare
Vittorio
V
Tocchini
Massimo
M
Bonsignori
Maurizio
M
Tonini
Giuseppe
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000097:blood*; D001859:Bone Neoplasms / Q000556:secondary; D016207:Cytokines / Q000096:biosynthesis; D004164:Diphosphonates / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000077211:Zoledronic Acid
D042501:Angiogenic Proteins; D016207:Cytokines; D004164:Diphosphonates; D007093:Imidazoles; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D000077211:Zoledronic Acid