INFLUENCE OF AN ANTI-ANGIOGENIC TREATMENT ON 9L GLIOSARCOMA - OXYGENATION AND RESPONSE TO CYTOTOXIC THERAPY

Tissue oxygen tensions were measured in subcutaneously growing rat 9L gliosarcoma under normal air and carbogen breathing conditions prior t o and after i.v. administration of a perflubron emulsion. When these a nimals were treated with the anti-angiogenic agents TNP-470 and minocy cline for 5 days prior to oxygen measurement, tumor hypoxia was decrea sed compared with untreated tumors. Hypoxia, defined as the percent of pO(2) readings less than or equal to 5 mm Hg, was decreased from 71% in untreated air-breathing controls to 34% in animals treated with the anti-angiogenic agents, the perflubron emulsion and carbogen breathin g. These effects were manifest in the increased response of the tumor to single-dose (10, 20 and 30 Gy) radiation therapy. Twenty-four hours after treatment with BCNU oxygenation of the tumors was not altered; however, 24 hr after administration of adriamycin oxygenation of the t umors was increased such that hypoxia in adriamycin-treated tumors in animals receiving the perflubron emulsion and carbogen was reduced to 21%. Tumor growth delay in the s.c. tumors was increased by the additi on of treatment with the anti-angiogenic agents from day 4 through day 18 post-tumor cell implantation along with BCNU or adriamycin on days 7-11. Administration of the perflubron emulsion and carbogen breathin g resulted in increased tumor growth delay with the chemotherapeutic a gents alone and in combination with the anti-angiogenic agents. Life s pan in animals bearing intracranially implanted 9L gliosarcoma progres sively increased with administration of the anti-angiogenic agents and then the anti-angiogenic agents and perflubron emulsion/carbogen comp ared to treatment with BCNU or adriamycin. (C) 1995 Wiley-Liss, Inc.