Preclinical studies of the combination of angiogenic inhibitors with cytotoxic agents

Y Kakeji, BA Teicher - Investigational new drugs, 1997 - Springer
Y Kakeji, BA Teicher
Investigational new drugs, 1997Springer
Abstract TNP-740, minocycline, suramin and genistein have demonstrated antiangiogenic
activity in various experimental systems. The effect of these agents alone and in two agent
combinations on the number of intratumoral vessels and response to cytotoxic anticancer
therapies was assessed in animals bearing the Lewis lung carcinoma. Treatment with each
of the antiangiogenic agents alone and in two agent combinations decreased the number of
intratumoral vessels visualized by CD31 or Factor VIII staining to 30% to 50% of the number …
Abstract
TNP-740, minocycline, suramin and genistein have demonstrated antiangiogenic activity in various experimental systems. The effect of these agents alone and in two agent combinations on the number of intratumoral vessels and response to cytotoxic anticancer therapies was assessed in animals bearing the Lewis lung carcinoma. Treatment with each of the antiangiogenic agents alone and in two agent combinations decreased the number of intratumoral vessels visualized by CD31 or Factor VIII staining to 30% to 50% of the number in the untreated control tumors. In general, the antiangiogenic agents are more effective adjuvants to cytotoxic therapies when used as two agent combinations than as single agents. The most effective antiangiogenic combinations were: TNP-470/minocycline > TNP-470/genistein > TNP-470/suramin. The increases in the response of the primary tumor to cyclophosphamide, adriamycin, CDDP, BCNU, x-rays or 5-fluorouracil and the lung metastases occur to about the same level with the addition of antiangiogenic agents to the therapies. With the treatment combination TNP-470/minocycline/cyclophosphamide 40% of the animals were cured. The results of these studies indicate that antiangiogenic agents can be very useful additions to treatment regimens for solid tumors.
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