Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

Abstract

Combretastatin A4 disodium phosphate (CA4DP) was evaluated in a xenograft model of AIDS-KS. KS xenografts were highly vascular, showing brisk mitotic activity, focal areas of necrosis, and intervening fibrovascular septae. Neoplastic cells were large or spindle-shaped, with vesicular nuclei and modest pleomorphism. Multiple junctions, microvillous-like projections, abortive lumina and rare Weibel Palade bodies were revealed by electron microscopy. Treatment with CA4DP (100 mg/kg) resulted in rapid onset of vascular effects that within 4 h resulted in an almost complete vascular shutdown in these tumors. Histological evaluation showed morphological damage within a few hours after treatment, followed by extensive necrosis which increased to ~ 90% by 24 h. At this time, viable tumor cells were evident only at the periphery of the tumor. These findings demonstrate not only the marked susceptibility of the KS model to CA4DP but also its potential application in studies related to the pathogenesis and therapy of AIDS-KS.