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• W4361942971 abstract "<div>Abstract<p><b>Purpose:</b> Antivascular endothelial growth factor therapy enhances the activity of radiotherapy in experimental models, and bevacizumab has therapeutic activity in patients with metastatic colorectal cancer.</p><p><b>Experimental Design:</b> Twenty-two patients with locally advanced inoperable colorectal carcinomas (LA/I-CRC) were treated with conformal hypofractionated (3.4 Gy/fraction 15) split-course accelerated radiotherapy (biological equivalent dose, 67.2 Gy) supported with amifostine, capecitabine (600 mg/m² daily, 5 days/week), and bevacizumab (5 mg/kg every 2 weeks, five cycles). Biopsies from nine patients, performed before and 1 week after bevacizumab administration, were analyzed for changes in mRNA expression with Illumina gene arrays.</p><p><b>Results:</b> No serious grade 3 chemotherapy-related side effects were recorded. There was low acute toxicity, with moist perineal desquamation noted in 2 of 22 patients, diarrhea grade 2 to 3 in 5 of 22 patients, and severe proctalgia in 2 of 22 patients. One patient died from Fournier's gangrene before treatment completion. Within a median follow-up of 18 months, two patients with preradiotheraphy direct involvement of adjacent organs expressed recto-vaginal/perineal fistula. Out of 19 evaluable cases, 13 (68.5) showed complete response and 4 showed (21.1) partial response. Fourteen patients are alive with no evidence of loco-regional relapse. In the gene array analysis, 30 known genes associated with transcription factors, DNA repair, and proliferation were downregulated by bevacizumab. DUSP1 gene was the most consistently downregulated transcript.</p><p><b>Conclusions:</b> The combination of radiotherapy with bevacizumab is feasible and results in a high rate of durable complete responses in patients with LA/I-CRC. Radiosensitization may occur through a direct effect on tumor cells followed by a wide scale suppression of transcription factors and genes involved in DNA repair and proliferation. (Clin Cancer Res 2009;15(22):706976)</p></div>" @default.
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• W4361942971 date "2023-03-31" @default.
• W4361942971 modified "2023-10-14" @default.
• W4361942971 title "Data from Phase I/II Trial of Bevacizumab and Radiotherapy for Locally Advanced Inoperable Colorectal Cancer: Vasculature-Independent Radiosensitizing Effect of Bevacizumab" @default.
• W4361942971 doi "https://doi.org/10.1158/1078-0432.c.6517453" @default.
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