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Title: Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results

Abstract

Purpose: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. Methods and Materials: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. Results: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m{sup 2} weekly,more » and capecitabine 625 mg/m{sup 2} bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. Conclusions: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further investigation with this regimen is being pursued in a Phase II setting.« less

Authors:
 [1];  [2];  [3];  [2];  [2];  [4];  [5];  [4];  [4];  [2];  [6];  [2]
  1. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States). E-mail: czito001@mc.duke.edu
  2. Department of Internal Medicine, Division of Medical Oncology and Transplantation, Duke University Medical Center, Durham, NC (United States)
  3. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)
  4. Department of General Surgery, Duke University Medical Center, Durham, NC (United States)
  5. Department of Radiology, Duke University Medical Center, Durham, NC (United States)
  6. Department of Biostatistics, Duke University Medical Center, Durham, NC (United States)
Publication Date:
OSTI Identifier:
20951667
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2007.02.001; PII: S0360-3016(07)00251-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ABSCESSES; CARCINOMAS; CHEMOTHERAPY; COMPUTERIZED TOMOGRAPHY; DIARRHEA; GROWTH FACTORS; MYOCARDIAL INFARCTION; PATIENTS; RADIATION DOSES; RADIOTHERAPY; RECTUM; SURGERY; TOXICITY

Citation Formats

Czito, Brian G., Bendell, Johanna C., Willett, Christopher G., Morse, Michael A., Blobe, Gerard C., Tyler, Douglas S., Thomas, John, Ludwig, Kirk A., Mantyh, Christopher R., Ashton, Jill, Yu Daohai, and Hurwitz, Herbert I.. Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2007.02.001.
Czito, Brian G., Bendell, Johanna C., Willett, Christopher G., Morse, Michael A., Blobe, Gerard C., Tyler, Douglas S., Thomas, John, Ludwig, Kirk A., Mantyh, Christopher R., Ashton, Jill, Yu Daohai, & Hurwitz, Herbert I.. Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results. United States. doi:10.1016/j.ijrobp.2007.02.001.
Czito, Brian G., Bendell, Johanna C., Willett, Christopher G., Morse, Michael A., Blobe, Gerard C., Tyler, Douglas S., Thomas, John, Ludwig, Kirk A., Mantyh, Christopher R., Ashton, Jill, Yu Daohai, and Hurwitz, Herbert I.. Fri . "Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results". United States. doi:10.1016/j.ijrobp.2007.02.001.
@article{osti_20951667,
title = {Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results},
author = {Czito, Brian G. and Bendell, Johanna C. and Willett, Christopher G. and Morse, Michael A. and Blobe, Gerard C. and Tyler, Douglas S. and Thomas, John and Ludwig, Kirk A. and Mantyh, Christopher R. and Ashton, Jill and Yu Daohai and Hurwitz, Herbert I.},
abstractNote = {Purpose: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. Methods and Materials: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. Results: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m{sup 2} weekly, and capecitabine 625 mg/m{sup 2} bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. Conclusions: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further investigation with this regimen is being pursued in a Phase II setting.},
doi = {10.1016/j.ijrobp.2007.02.001},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 68,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}