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

Brian G. Czito, Johanna C. Bendell, Christopher G. Willett, Michael A. Morse, Gerard C. Blobe, Douglas Tyler, John Thomas, Kirk A. Ludwig, Christopher R. Mantyh, Jill Ashton, Daohai Yu, Herbert I. Hurwitz

Research output: Contribution to journalArticle

119 Citations (Scopus)

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/m2 weekly, and capecitabine 625 mg/m2 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.

Original languageEnglish (US)
Pages (from-to)472-478
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume68
Issue number2
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

oxaliplatin
Rectal Neoplasms
radiation therapy
Radiotherapy
cancer
therapy
toxicity
dosage
chemotherapy
Adjuvant Chemotherapy
Vascular Endothelial Growth Factor A
Colorectal Neoplasms
tumors
Endpoint Determination
myocardial infarction
Bevacizumab
Capecitabine
rectum

Keywords

  • Bevacizumab
  • Capecitabine
  • Oxaliplatin
  • Radiation therapy
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer : Phase I Trial Results. / Czito, Brian G.; Bendell, Johanna C.; Willett, Christopher G.; Morse, Michael A.; Blobe, Gerard C.; Tyler, Douglas; Thomas, John; Ludwig, Kirk A.; Mantyh, Christopher R.; Ashton, Jill; Yu, Daohai; Hurwitz, Herbert I.

In: International Journal of Radiation Oncology Biology Physics, Vol. 68, No. 2, 01.06.2007, p. 472-478.

Research output: Contribution to journalArticle

Czito, BG, Bendell, JC, Willett, CG, Morse, MA, Blobe, GC, Tyler, D, Thomas, J, Ludwig, KA, Mantyh, CR, Ashton, J, Yu, D & Hurwitz, HI 2007, 'Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results', International Journal of Radiation Oncology Biology Physics, vol. 68, no. 2, pp. 472-478. https://doi.org/10.1016/j.ijrobp.2007.02.001
Czito, Brian G. ; Bendell, Johanna C. ; Willett, Christopher G. ; Morse, Michael A. ; Blobe, Gerard C. ; Tyler, Douglas ; 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. In: International Journal of Radiation Oncology Biology Physics. 2007 ; Vol. 68, No. 2. pp. 472-478.
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AU - Morse, Michael A.

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