Skip to main content

Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study.

Publication ,  Journal Article
Willett, CG; Duda, DG; di Tomaso, E; Boucher, Y; Ancukiewicz, M; Sahani, DV; Lahdenranta, J; Chung, DC; Fischman, AJ; Lauwers, GY; Shellito, P ...
Published in: J Clin Oncol
June 20, 2009

PURPOSE: To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response. PATIENTS AND METHODS: In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m(2)/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy. RESULTS: Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuarial 5-year local control and overall survival of 100%. Actuarial 5-year disease-free survival was 75% and five patients developed metastases postsurgery. Bevacizumab with chemoradiotherapy showed acceptable toxicity. Bevacizumab decreased tumor interstitial fluid pressure and blood flow. Baseline plasma soluble vascular endothelial growth factor receptor 1 (sVEGFR1), plasma vascular endothelial growth factor (VEGF), placental-derived growth factor (PlGF), and interleukin 6 (IL-6) during treatment, and circulating endothelial cells (CECs) after treatment showed significant correlations with outcome. CONCLUSION: Bevacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer. Plasma VEGF, PlGF, sVEGFR1, and IL-6 and CECs should be further evaluated as candidate biomarkers of response for this regimen.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

June 20, 2009

Volume

27

Issue

18

Start / End Page

3020 / 3026

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Rectal Neoplasms
  • Oncology & Carcinogenesis
  • Neoadjuvant Therapy
  • Middle Aged
  • Male
  • Interleukin-6
  • Humans
  • Fluorouracil
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Willett, C. G., Duda, D. G., di Tomaso, E., Boucher, Y., Ancukiewicz, M., Sahani, D. V., … Jain, R. K. (2009). Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol, 27(18), 3020–3026. https://doi.org/10.1200/JCO.2008.21.1771
Willett, Christopher G., Dan G. Duda, Emmanuelle di Tomaso, Yves Boucher, Marek Ancukiewicz, Dushyant V. Sahani, Johanna Lahdenranta, et al. “Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study.J Clin Oncol 27, no. 18 (June 20, 2009): 3020–26. https://doi.org/10.1200/JCO.2008.21.1771.
Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol. 2009 Jun 20;27(18):3020–6.
Willett, Christopher G., et al. “Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study.J Clin Oncol, vol. 27, no. 18, June 2009, pp. 3020–26. Pubmed, doi:10.1200/JCO.2008.21.1771.
Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, Lahdenranta J, Chung DC, Fischman AJ, Lauwers GY, Shellito P, Czito BG, Wong TZ, Paulson E, Poleski M, Vujaskovic Z, Bentley R, Chen HX, Clark JW, Jain RK. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol. 2009 Jun 20;27(18):3020–3026.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

June 20, 2009

Volume

27

Issue

18

Start / End Page

3020 / 3026

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Rectal Neoplasms
  • Oncology & Carcinogenesis
  • Neoadjuvant Therapy
  • Middle Aged
  • Male
  • Interleukin-6
  • Humans
  • Fluorouracil
  • Female