Fluoropyrimidine (5-fluorouracil [5-FU] is the oldest chemotherapy drug for colon cancer and it is usually given with leucovorin [LV]. For second or third line therapy, single agents are acceptable and NCCN has a complex schema when to give what for second line and also lists Erbitux and Vectbix. Capecitabine is also FDA approved as a single agent. NCCN does not list 5FU/Leukovorin but it can also be considered appropriate given the long history of its use for colorectal metastatic cancer and support from many older papers.
The issue of the best schedule for 5FU.leukovorin has not been resolved, and with the appearance of many new drugs, has receded into the past and is no longer being investigated. Both high dose leukovorin (Mayo) and low dose leukovorin dosing is effective but the former apears to be more toxic. The Mayo Clinic schedule is 5-FU bolus 425 mg/m2 plus LV 20 mg/m2 daily for 5 days, repeated every 45 weeks for six cycles. This was superior to control in NCCTG Trial 87-46-51 , and at least equivalent to three other regimens in the large US Intergroup trial INT-0089. Older evidence from phase II trials suggests that weekly 5-fluorouracil and leucovorin have lower toxicity(3).
The FDA has not weigned in on the schedule. The indicaiton states that Fluorouracil is effective in the palliative management of carcinoma of the colon, rectum, breast, stomach and pancreas.
1.Boige V, Mendiboure J, Pignon JP, et al. Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. J Clin Oncol 2010; 28:2556.
2.Goldberg RM, Rothenberg ML, Van Cutsem E, et al. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist 2007; 12:38.
3.K. Patel, D. A. Anthoney, A. M. Crellin, D. Sebag-Montefiore, J. Messruther and M. T. Seymour, Weekly 5-fluorouracil and leucovorin: achieving lower toxicity with higher dose-intensity in adjuvant chemotherapy after colorectal cancer resection Ann Oncol (2004) 15 (4): 568-573.
4.Meta-analysis Group in Cancer. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol1998; 16: 35373541
5.Florouracyo infusion, Prescribing Information, 2012
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