Accession Number:

ADA393392

Title:

Radiation-Induced Chemosensitization Potentiation of Antitumor Activity of Polymer-Drug Conjugates

Descriptive Note:

Annual rept. 1 Apr 2000-31 Mar 2001

Corporate Author:

M D ANDERSON CANCER CENTER HOUSTON TX

Personal Author(s):

Report Date:

2001-04-01

Pagination or Media Count:

28.0

Abstract:

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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research
  • Radiobiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE