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
Clinical Trial
. 2012 Dec 10;30(35):4344-51.
doi: 10.1200/JCO.2012.43.8085. Epub 2012 Nov 13.

Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin

Leonard L Gunderson  1 , Kathryn A Winter, Jaffer A Ajani, John E Pedersen, Jennifer Moughan, Al B Benson 3rd, Charles R Thomas Jr, Robert J Mayer, Michael G Haddock, Tyvin A Rich, Christopher G Willett
Affiliations
Clinical Trial

Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin

Leonard L Gunderson et al. J Clin Oncol. .

Abstract

Purpose: On initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse (locoregional failure [LRF], distant metastasis) in this patient group.

Patients and methods: Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors.

Results: Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS.

Conclusion: CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.

Trial registration: ClinicalTrials.gov NCT00003596.

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. ANC, absolute neutrophil count; HGB, hemoglobin.
Fig 2.
Fig 2.
Impact of radiation therapy plus fluorouracil/mitomycin (RT + FU/MMC) v radiation therapy plus fluorouracil/cisplatin (RT + FU/CDDP) on (A) disease-free survival (P = .006) and (B) overall survival (P = .026). HR, hazard ratio.
Fig 3.
Fig 3.
Impact of radiation therapy plus fluorouracil/mitomycin (RT + FU/MMC) v radiation therapy plus fluorouracil/cisplatin (RT + FU/CDDP) on (A) locoregional failure (P = .087) and (B) distant failure (P = .12). HR, hazard ratio.
Fig 4.
Fig 4.
Impact of radiation therapy plus fluorouracil/mitomycin (RT + FU/MMC) v radiation therapy plus fluorouracil/cisplatin (RT + FU/CDDP) on (A) colostomy-free survival (P = .05) and (B) colostomy failure (P = .074). HR, hazard ratio.
See this image and copyright information in PMC

References

    1. Nigro ND, Seydel HG, Considine B, et al. Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Cancer. 1983;51:1826–1829. - PubMed
    1. Sischy B, Doggett RL, Krall JM, et al. Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: Interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst. 1989;81:850–856. - PubMed
    1. Cummings BJ, Keane TJ, O'Sullivan B, et al. Epidermoid anal cancer: Treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys. 1991;21:1115–1125. - PubMed
    1. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: Results of a phase III randomized intergroup study. J Clin Oncol. 1996;14:2527–2539. - PubMed
    1. [No authors listed]: Epidermoid anal cancer: Results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin: UKCCCR Anal Cancer Trial Working Party—UK Co-ordinating Committee on Cancer Research. Lancet. 1996;348:1049–1054. - PubMed

Publication types

MeSH terms

Associated data