Ly. Li et al., TARGETING THE TUMOR VASCULATURE WITH COMBRETASTATIN A-4 DISODIUM PHOSPHATE - EFFECTS ON RADIATION-THERAPY, International journal of radiation oncology, biology, physics, 42(4), 1998, pp. 899-903
Citations number
20
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
Purpose: The aim of this study was to evaluate the antitumor efficacy
of combretastatin A-4 disodium phosphate (combretastatin prodrug) in t
he rodent KHT sarcoma model either alone or in combination with radiat
ion therapy. Methods: KHT tumors were grown in C3H/HeJ mice, Combretas
tatin A-4 prodrug was injected intraperitoneally at doses ranging from
10 to 100 mg/kg, Tumors were irradiated in unanesthetized mice using
a Cs-137 source, Tumor response to combretastatin A-4 prodrug was asse
ssed by histological evaluations as well as an in vivo to in vitro cel
l survival assay. Results: Histological evaluation showed morphologica
l damage of tumor cells within a few hours after drug treatment, follo
wed by extensive central necrosis, Administering increasing doses of c
ombretastatin A-4 prodrug to tumor-bearing mice resulted in a dose-dep
endent increase in cell killing irrespective of whether the tumors wer
e irradiated or not. When combined with radiation, a 100 mg/kg dose of
combretastatin A-4 prodrug reduced tumor cell survival 10-500-fold lo
wer than that seen with radiation alone. Further, the shape of the cel
l survival curve observed following the combination therapy suggested
that including combretastatin in the treatment had a major effect on t
he radiation-resistant hypoxic cell subpopulation associated with this
tumor. Conclusion: The present results demonstrated that in the KHT s
arcoma, combretastatin A-4 prodrug caused rapid vascular shutdown, a c
oncentration-dependent direct cell killing, and effective enhancement
of the antitumor effects of radiation therapy. (C) 1998 Elsevier Scien
ce Inc.