Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2013 Jan 20;31(3):359-64.
doi: 10.1200/JCO.2012.44.4711. Epub 2012 Dec 10.

Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial

Carmen J Allegra  1 , Greg Yothers, Michael J O'Connell, Saima Sharif, Nicholas J Petrelli, Samia H Lopa, Norman Wolmark
Affiliations
Randomized Controlled Trial

Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial

Carmen J Allegra et al. J Clin Oncol. .

Abstract

Purpose: The National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time.

Patients and methods: Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point.

Results: Of 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value <.0001). The secondary end point of OS was no different between the two study arms for all patients (HR, 0.95; 95% CI, 0.79 to 1.13; P = .56) and for those with stage 3 disease (HR, 1.0; 95% CI, 0.83 to 1.21; P = .99).

Conclusion: Bevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.

Trial registration: ClinicalTrials.gov NCT00096278.

PubMed Disclaimer

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. DFS, disease-free survival; mFF6, modified fluorouracil, leucovorin, and oxaliplatin for 6 months; mFF6 + Bev, mFF6 for 6 months plus bevacizumab for 12 months; OS, overall survival.
Fig 2.
Fig 2.
Disease-free survival (DFS). Overall DFS for patients treated with modified fluorouracil, leucovorin, and oxaliplatin (mFF6) alone for 6 months or mFF6 for 6 months plus bevacizumab for 12 months (mFF6 + Bev). HR, hazard ratio.
Fig 3.
Fig 3.
Overall survival for all patients treated with modified fluorouracil, leucovorin, and oxaliplatin (mFF6) alone for 6 months or mFF6 for 6 months plus bevacizumab for 12 months, (mFF6 + Bev). HR, hazard ratio.
Fig 4.
Fig 4.
Survival after recurrence for patients relapsing (A) within the first 18 months after study entry and (B) relapsing 18 months after study entry. HR, hazard ratio; mFF6, modified fluorouracil, leucovorin, and oxaliplatin for 6 months; mFF6 + Bev, mFF6 for 6 months plus bevacizumab for 12 months.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. André T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med . 2004;350:2343–2351. - PubMed
    1. Kuebler JP, Wieand HS, O'Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: Results from NSABP C-07. J Clin Oncol . 2007;25:2198–2204. - PubMed
    1. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol . 2007;25:1539–1544. - PubMed
    1. Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study. J Clin Oncol. 2008;26:2013–2019. [Errata: J Clin Oncol 26:3110, 2008 and J Clin Oncol 27:653, 2009] - PubMed
    1. Kozloff M, Yood MU, Berlin J, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: The BRiTE observational cohort study. Oncologist . 2009;14:862–870. - PubMed

Publication types

MeSH terms

Supplementary concepts

Associated data