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
Comparative Study
. 2013 Oct 10;31(29):3656-63.
doi: 10.1200/JCO.2013.49.4344. Epub 2013 Aug 26.

Comparison of outcomes after fluorouracil-based adjuvant therapy for stages II and III colon cancer between 1978 to 1995 and 1996 to 2007: evidence of stage migration from the ACCENT database

Qian Shi  1 , Thierry Andre, Axel Grothey, Greg Yothers, Stanley R Hamilton, Brian M Bot, Daniel G Haller, Eric Van Cutsem, Chris Twelves, Jacqueline K Benedetti, Michael J O'Connell, Daniel J Sargent
Affiliations
Comparative Study

Comparison of outcomes after fluorouracil-based adjuvant therapy for stages II and III colon cancer between 1978 to 1995 and 1996 to 2007: evidence of stage migration from the ACCENT database

Qian Shi et al. J Clin Oncol. .

Abstract

Purpose: With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens.

Methods: Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage.

Results: Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages.

Conclusion: Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients.

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.
In patients with (A, B) stage II and (C, D) stage III disease, (A, C) recurrence and (B, D) mortality rates by time since random assignment. Risk of recurrence was calculated as the number of recurrences within each of the 6-month windows divided by the number of patients at risk (recurrence free) at the start of each interval. Risk of mortality was calculated in the same fashion.
Fig 2.
Fig 2.
Comparison of clinical outcomes between newer- and old-era trials. In patients with (A, C, E) stage II and (B, D, F) stage III disease, (A, B) time to recurrence, (E, F) time from recurrence to death, and (C, D) overall survival. HR, hazard ratio; KM Est, event-free rate at given time point (36 or 60 months) estimated based on Kaplan-Meier method.
Fig 3.
Fig 3.
Comparison of time to recurrence stratified by time era and lymph nodes (LNs) examined in patients with (A) stage II and (B) stage III disease. KM Est, event-free rate at given time point (36 or 60 months) estimated based on Kaplan-Meier method.
Fig A1.
Fig A1.
Comparison of outcomes between time eras (newer v old) by subpopulation for (A) time to recurrence, (B) time from recurrence to death, and (C) overall survival.
See this image and copyright information in PMC

References

    1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. - PubMed
    1. Edwards BK, Ward E, Kohler BA, et al. Report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116:544–573. - PMC - PubMed
    1. Desch CE, Benson AB, 3rd, Somerfield MR, et al. Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2005;23:8512–8519. - PubMed
    1. Petrelli N, Douglass HO, Jr, Herrera L, et al. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: A prospective randomized phase III trial—Gastrointestinal Tumor Study Group. J Clin Oncol. 1989;7:1419–1426. - PubMed
    1. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer. Evidence in terms of response rate—Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol. 1992;10:896–903. - PubMed

Publication types