This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schilsky, R. L. Articles by Pazdur, R. Search for Related Content PubMed PubMed Citation Articles by Schilsky, R. L. Articles by Pazdur, R. Social Bookmarking                            What's this?

Randomized, Open-Label, Phase III Study of a 28-Day Oral Regimen of Eniluracil Plus Fluorouracil Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Therapy in Patients With Metastatic/Advanced Colorectal Cancer

From the University of Chicago, Chicago, IL; GlaxoSmithKline, Research Triangle Park, NC; Response Oncology, Inc, Memphis, TN; Tom Baker Cancer Centre, Calgary, Alberta, Nova Scotia Cancer Center, Halifax, Nova Scotia, and Montreal General Hospital, Montreal, Ontario, Canada; Michiana Hematology-Oncology, South Bend, IN; and University of Texas, M.D. Anderson Cancer Center, Houston, TX.

Address reprint requests to Richard L. Schilsky, MD, Biological Sciences Division, The University of Chicago, 5841 S. Maryland Ave, Chicago, IL 60637-1463.

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer.

PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m²/1.15 mg/m² twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m²/20 mg/m² once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point.

RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P = .01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P = .354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients.

CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.

The views expressed herein are the result of independent work and are not the opinion of the Food and Drug Administration.)

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. L. Yen-Revollo, R. M. Goldberg, and H. L. McLeod Can Inhibiting Dihydropyrimidine Dehydrogenase Limit Hand-Foot Syndrome Caused by Fluoropyrimidines? Clin. Cancer Res., January 1, 2008; 14(1): 8 - 13. [Abstract] [Full Text] [PDF]

				B. Freidlin, E. L. Korn, S. L. George, and R. Gray Randomized Clinical Trial Design for Assessing Noninferiority When Superiority Is Expected J. Clin. Oncol., November 1, 2007; 25(31): 5019 - 5023. [Abstract] [Full Text] [PDF]

				P. A. Tang, S. M. Bentzen, E. X. Chen, and L. L. Siu Surrogate End Points for Median Overall Survival in Metastatic Colorectal Cancer: Literature-Based Analysis From 39 Randomized Controlled Trials of First-Line Chemotherapy J. Clin. Oncol., October 10, 2007; 25(29): 4562 - 4568. [Abstract] [Full Text] [PDF]

				L. S. Rosen, E. Abdi, I. D. Davis, J. Gutheil, F. M. Schnell, J. Zalcberg, A. Cesano, U. Gayko, M.-G. Chen, and S. Clarke Palifermin Reduces the Incidence of Oral Mucositis in Patients With Metastatic Colorectal Cancer Treated With Fluorouracil-Based Chemotherapy J. Clin. Oncol., November 20, 2006; 24(33): 5194 - 5200. [Abstract] [Full Text] [PDF]

				J. Sakamoto, C. Hamada, M. Rahman, S. Kodaira, K. Ito, H. Nakazato, Y. Ohashi, and M. Yasutomi An Individual Patient Data Meta-analysis of Adjuvant Therapy with Carmofur in Patients with Curatively Resected Colon Cancer Jpn. J. Clin. Oncol., September 1, 2005; 35(9): 536 - 544. [Abstract] [Full Text] [PDF]

				A. Iop, A. M. Manfredi, and S. Bonura Fatigue in cancer patients receiving chemotherapy: an analysis of published studies Ann. Onc., May 1, 2004; 15(5): 712 - 720. [Abstract] [Full Text] [PDF]

				D. Yip, C. Karapetis, A. H. Strickland, C. Steer, C. Holford, S. Knight, and P. Harper A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies Ann. Onc., June 1, 2003; 14(6): 864 - 866. [Abstract] [Full Text] [PDF]

				I. Chau and D. Cunningham Chemotherapy in colorectal cancer: new options and new challenges Br. Med. Bull., December 1, 2002; 64(1): 159 - 180. [Abstract] [Full Text] [PDF]

				T. J. Hobday, J. W. Kugler, M. R. Mahoney, D. J. Sargent, J. A. Sloan, T. R. Fitch, J. E. Krook, M. J. O'Connell, J. A. Mailliard, M. T. Tirona, et al. Efficacy and Quality-of-Life Data Are Related in a Phase II Trial of Oral Chemotherapy in Previously Untreated Patients With Metastatic Colorectal Carcinoma J. Clin. Oncol., December 1, 2002; 20(23): 4574 - 4580. [Abstract] [Full Text] [PDF]