Radiation-Induced Chemosensitization Potentiation of Antitumor Activity of Polymer-Drug Conjugates
Annual rept. 1 Apr 2000-31 Mar 2001
M D ANDERSON CANCER CENTER HOUSTON TX
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Although combined chemotherapy and radiotherapy has produced significantly improved response and survival rates among cancer patients, there is still a compelling need to establish the most effective way to deliver these agents. The ultimate goal of this study is to develop a more effective treatment regimen for preventing both systemic relapse and local-regional recurrence in breast cancer patients. We hypothesize that radiation enhances the antitumor activity of polymer-drug conjugates by increasing tumor vascular permeability and thus enhancing the tumor uptake of PG-TXL. Using a water-soluble polyL-glutamic acid-conjugated paclitaxel PG-TXL as a model compound, we demonstrated that combined radiation and PG-TXL produced a significantly greater tumor growth delay than treatment with combined radiation and paclitaxel. Furthermore, supperadditive interaction with enhancement factors ranging from 2.0 to 4.3 was also observed when PG-TXL was given 4-72 hr before tumor irradiation, suggesting that PG-TXL may in turn sensitize tumor response toward radiation. Our data support a treatment strategy combining radiation and polymeric chemotherapy that may have important clinical implications in terms of scheduling and optimization of the therapeutic ratio.
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