Pamidronate induces modifications of circulating angiogenetic factors in cancer patients.
OBJECTIVE
Recently, new experimental data suggested that, besides inhibiting osteoclasts, bisphosphonate may also have an antitumor effect. Antiangionetetic activity is one of the possible mechanisms of anticancer activity attributed to bisphosphonates. The purpose of this study was to evaluate the modifications in angiogenic cytokines levels after pamidronate infusion.


METHODS
Twenty-five consecutive cancer patients with bone metastases treated monthly with disodium pamidronate infusion were evaluated prospectively for circulating levels of vascular endothelial growth factor (VEGF), gamma-IFN, interleukin (IL)-6, and IL-8 at different time points: just before and after 1, 2, and 7 days after pamidronate infusion.


RESULTS
Basal VEGF levels decreased significantly 1, 2, and 7 days after pamidronate infusion. gamma-IFN and IL-6 levels increased 1 day after the infusion but rapidly decreased after 2 days. Moreover, our data showed a statistically significant negative correlation between VEGF and gamma-IFN levels (P < 0.0001) and a positive correlation between VEGF and IL-8 (P = 0.04).


CONCLUSIONS
This study confirms that pamidronate could have antiangiogenic properties through a significant and lasting decrease of VEGF serum levels.
Santini
Daniele
D
Università Campus Bio-Medico, 00155 Rome, Italy.
Vincenzi
Bruno
B
Avvisati
Giuseppe
G
Dicuonzo
Giordano
G
Battistoni
Fabrizio
F
Gavasci
Michele
M
Salerno
Alfredo
A
Denaro
Vincenzo
V
Tonini
Giuseppe
G
D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000097:blood; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D016014:Linear Models; D008222:Lymphokines / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D000077268:Pamidronate; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D000970:Antineoplastic Agents; D016207:Cytokines; D004164:Diphosphonates; D016228:Endothelial Growth Factors; D015850:Interleukin-6; D016209:Interleukin-8; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007371:Interferon-gamma; D000077268:Pamidronate