Abstract
Oral chemotherapy offers several potential benefits over intravenous treatment, and the majority of patients would prefer oral therapy provided that it does not compromise efficacy. We review the evidence that oral fluoropyrimidines can replace intravenous 5-fluorouracil (5-FU) in the adjuvant therapy of colon cancer, without loss of efficacy, while at the same time improving tolerability and reducing the use of medical resources. The addition of oxaliplatin to intravenous 5-FU improves disease-free survival in patients with resected colon cancer and both uracil/tegafur and capecitabine can be combined safely with oxaliplatin. The effect on efficacy of replacing intravenous 5-FU with oral fluoropyrimidines in combination regimens is being assessed in ongoing trials.
Similar content being viewed by others
References and Recommended Reading
Francini G, Petrioli R, Lorenzini L, et al.: Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology 1994, 106:899–906.
O’Connell MJ, Mailliard JA, Kahn MJ, et al.: Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer.J Clin Oncol 1997, 15:246–250.
Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet 1995, 345:939–944.
Borner MM, Schoffski P, e Wit R, et al.: Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002, 38:349–358.
Liu G, Franssen E, Fitch MI, Warner E: Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997, 15:110–115.
van Cutsem E, Hoff PM, Harper P, et al.: Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials.Br J Cancer 2004, 90:1190–1197. Evidence that capecitabine could replace intravenous 5-FU without loss of efficacy in advanced disease.
Cassidy J, Twelves C, Van Cutsem E, et al.: First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin.Ann Oncol 2002, 13:566–575.
Twelves C, Wong A, Nowacki MP, et al.: Capecitabine as adjuvant treatment for stage III colon cancer.N Engl J Med 2005, 352:2696–2704. Demonstration that capecitabine can replace intravenous bolus 5- FU in patients with resected colon cancer with equivalent efficacy and favorable toxicity profile.
Scheithauer W, McKendrick J, Begbie S, et al.: Oral capecitabine as an alternative to IV 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial.Ann Oncol 2003, 14:1735–1743.
Welves C, Wong A, Nowacki M, et al.: Updated efficacy findings from the X-ACT phase III trial of capecitabine (X) vs. bolus 5-FU/LV as adjuvant therapy for patients (pts) with Dukes’ C colon cancer [abstract].Presented at the 41st Annual Meeting of the American Society of Clinical Oncology. Orlando, FL; May 13–17, 2005.
Díaz-Rubio E, Burris H, Douillard JY, et al.: On behalf of the X-Act Study Group, Safety of capecitabine (X) compared to fluorouracil/leucovorin (5-FU/LV) for the adjuvant treatment of elderly colon cancer patients (pts) [abstract].Prog Proc Am Soc Clin Oncol 2004, 23:304.
Twelves C, Boyer M, Findlay M, et al.: Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. Eur J Cancer 2001, 37:597–604. Evidence for the health economic beneifits of using capecitabine.
Douillard JY: Ann Oncol 2004, 15:73.
Andre T, Boni C, Mounedji-Boudiaf L, etal.: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.N Engl J Med 2004, 350:2343–2351. Withmark et al. [15], two studies demonstrating improvement in disease-free survival with the addition of oxaliplatin to 5-FU/LV for patients with resected colon cancer.
Wolmark N, Wieand HS, Kuebler JP, et al.: A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: results of NSABP Protocol C-07 [abstract] Proc Am Soc Clin Oncol 2005, 23:3500. With Andre etal. [14], two studies demonstrating improvement in disease-free survival with the addition of oxaliplatin to 5-FU/LV for patients with resected colon cancer.
Cassidy J, Tabernero J, Twelves C, et al.: XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer.J Clin Oncol 2004, 22:2084–2091.
Schmoll HJ, Tabernero J, Nowacki M, et al.: Safety findings from a randomized phase III trial of capecitabine + oxaliplatin (XELOX) versus bolus 5-FU/LV as adjuvant therapy for patients (pts) with stage III colon cancer [abstract].Presented at the American Society for Clinical Oncology Gastrointestinal Cancers Symposium.San Francisco, CA; January 26–28, 2006. Demonstration that oxaliplatin and capecitabine can feasibly and safely be combined as adjuvant therapy for patients with stage III colon cancer.
Cassidy J, Bjarnason GA, Hickish T, et al.: Randomized double blind (DB) placebo (Plcb) controlled phase III study assessing the efficacy of xaliproden (X) in reducing the cumulative peripheral sensory neuropathy (PSN) induced by the oxaliplatin (Ox) and 5-FU/LV combination (FOLFOX4) in first line treatment of patients (pts) with metastatic colorectal cancer (MCRC) [abstract]. Presented at the American Society for Clinical Oncology Gastrointestinal Cancers Symposium. San Francisco, CA; January 26–28, 2006.
Sanchiz F, Milla A: Tegafur-uracil (UFT) plus folinic acid in advanced rectal cancer.Jpn J Clin Oncol 1994, 24:322–326.
Pazdur R, Lassere Y, Rhodes V, et al.: Phase II trial of uracil and tegafur plus oral leucovorin: an effective oral regimen in the treatment of metastatic colorectal carcinoma. J Clin Oncol 1994, 12:2296–3000.
Carmichael J, Popiela T, Radstone D, et al.: Randomized comparative study of tegafur/uracil and oral leucovorin versus parenteral fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.J Clin Oncol 2002, 20:3617–3627.
Douillard JY, Hoff PM, Skillings JR, et al., Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.J Clin Oncol 2002, 20:3605–3616.
Piedbois P, Calais G, Fric D, Facchini T: Compliance with tegafur-uracil/leucovorin treatment in advanced colorectal cancer from the patient and physician perspective: results from a French registry [abstract].Presented at the American Society for Clinical Oncology Gastrointestinal Cancers Symposium. San Francisco, CA; January 26–28, 2006.
Sulkes A, Benner SE, Canetta RM: Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.J Clin Oncol 1998, 16:3461–3475.
Nakazato H, Koike A, Saji S, et al.: Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: a prospective randomized clinical trial [abstract].Prog Proc Am Soc Clin Oncol 1997, 16:279a.
Fujii M, Kochi M, Sawa H, et al.: Preoperative and postoperative adjuvant chemotherapy for colorectal cancer- results of 5-year survival using UFT. A pilot study. J Jpn Soc Cancer Ther 1995, 30:584–594.
Mitomi T, Tsuchiya S, Hiki Y: A randomized controlled study on adjuvant chemotherapy with UFT in curatively resected colorectal cancer [abstract].Prog Proc Am Soc Clin Oncol 1993, 12:690.
Wolmark N, Wieand S, Kuebler JP, et al.: A phase III trial comparing oral UFT to FULV in stage II and III carcinoma of the colon: results of NSABP Protocol C-06 [abstract]. Proceedings from the 41st Annual Meeting of the American Society of Clinical Oncology. Orlando, FL; May 13–17, 2005. Demonstration that UFT/LV is equivalent to intravenous 5-FU/LV in patients with resected colon cancer. It did not demonstrate a benefit in terms of toxicity.
Yothers G, Kopec JA, Ganz PA, et al.: A comparison of quality of life in colon cancer patients receiving adjuvant uracil/ftorafur + leucovorin versus 5-fluorouracil + leucovorin in NSABP C-06 [abstract].Proc Am Soc Clin Oncol 2005, 23:8080.
Feliu J, Vicent JM, Garcia-Giron C, et al.: Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer.Br J Cancer 2004, 91:1758–1762.
Bennouna J, Perrier H, Paillot B, et al.: A phase II study of oral uracil/ftorafur (UFT) plus leucovorin combined with oxaliplatin (TEGAFOX) as first-line treatment in patients with metastatic colorectal cancer.Br J Cancer 2006, 94:69–73.
Shirasaka T, Shimamoto Y, Fukushima M: Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats.Cancer Res 1993, 53:4004–4009.
Ohtsu A, Baba H, Sakata Y, et al.: Phase II study of S-1, a novel oral fluoropyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group.Br J Cancer 2000, 83:141–145.
Van den Brande J, Schoffski P, Schellens JH, et al.: EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer. Br J Cancer 2003, 88:648–653.
Shirao K, Hoff PM, Ohtsu A, etal.: Comparison of the efficacy, toxicity, and pharmacokinetics of a uracil/tegafur (UFT) plus oral leucovorin (LV) regimen between Japanese and American patients with advanced colorectal cancer: joint United States and Japan study of UFT/LV. J Clin Oncol 2004, 22:3466–3474.
Ajani JA, Faust J, Ikeda K, et al.: Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma.J Clin Oncol 2005, 23:6957–6965.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Glasspool, R.M., Cassidy, J. Oral fluoropyrimidines in the adjuvant therapy of colon cancer. Curr colorectal cancer rep 2, 137–141 (2006). https://doi.org/10.1007/s11888-006-0032-9
Issue Date:
DOI: https://doi.org/10.1007/s11888-006-0032-9