Chemoradiotherapy improves survival for some cancer patients. Methods of enhancing treatment response would further enhance survival rates. The effect of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not previously been examined. C57B16 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells into the flank and randomized to 1 of 10 treatment groups when tumor volume approached 1000 mm(3). Animals received combinations of standard doses of intraperitoneal cisplatin, 5-fluorouracil, and the antiangiogenic agent genistein, together with 10 or 20 Gy of external beam radiotherapy. Animals were sacrificed at day 6 when tumor volume, microvessel density, and serum VEGF were determined. Mean (SEM) tumor volume in the chemoradiotherapy group was 762 (212) mm(3) versus 565 (79) mm(3) in the chemoradiotherapy plus genistein group (P = 0.04, unpaired t-test). The addition of genistein produced a significant reduction in tumor microvessel density (P = 0.01) as well as serum VEGF levels (P < 0.05) compared to those animals receiving chemoradiation alone. This study provides proof of principle that chemoradiation can be enhanced by the addition of an antiangiogenic agent to the regime and suggests that further examination of such regimes is warranted.
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