5-fluorouracil colorectal cancer

Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovor-in for metastatic colorectal cancer. N Engl J Med 350 2335-2342... 

Fluorouracil-based chemotherapy is the standard of care for the adjuvant treatment of colorectal cancer either as a single agent or, more commonly, in combination with other agents. 5-Fluorouracil (5-FU) alone results in a small improvement in survival that can vary based on the method of 5-FU administration. Studies suggest that protracted or continuous intravenous (IV) 5-FU infusion treatment schedules are more effective than bolus therapy.20... 

Goldberg RM, Sargent DJ, Morton RF, et al. A randomized, controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004 22 23-30. 

Saltz LB, Cox JV, Blanke C et al. Irino-tecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000 343 905-914. 

Gamelin E, Boisdron-Celle M, Guer-in-Meyer V et al. Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer a potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J Clin Oncol 1999 17 1105-1110. 

Leichman CG, Lenz HJ, Leichman L, Danenberg K, Baranda J, Groshen S et al. Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol 1997 15 3223-3229. 

Fluorouracil (5-FU) is the most widely used chemotherapeutic agent for colorectal cancer. Leucovorin (folinic acid) is usually added to 5-FU as a biochemical modulator to improve response rates. 

Giacchetti, S. et al. Phase III multicenter randomized trial of oxaUplatm added to chronomod-ulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer,. Clin. Oncol, 18, 136-147, 2000. 

Cunningham, D. et al.. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. The Lancet, 352, 1413-1418, 1998. 

Fluorouracil (5-FU) is a major drug in the treatment of advanced colorectal cancer. Of the administered 5-FU, 70-80% is degraded by DPD in vivo to dihydrofluorouracil. 

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths in the United States. (77). The incidence is approx. 40 per 100,000 in men and 25-30 per 100,000 in women (78). For those with stage 111 disease with presumed micrometastatic disease, adjuvant chemotherapy is used, typically 5-fluorouracil (5-FU) and leucovorin for 6-8 mo, with a 30% reduction in disease recurrence and 22-32% reduction in mortality (79,80). 

In combination with 5-fluorouracil (5-FU) to prolong survival in the palliative treatment of patients with advanced colorectal cancer. 

Oxaliplatin (trans-L-diaminocyclohexane oxalate platinum II) was selected for development based on preclinical antitumor activity in murine leukemia lines and in colon cancer models (151,152). The clinical development of oxaliplatin has been primarily in colorectal cancer alone and in combination with 5-fluorouracil. 

Meta-Analysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998 16( 1 ) 301—308. 

Levi F, Zidani R, Misset JL. Randomized multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet 1997 350 681-686. 

Oxaliplatin is a newer platinum-based agent. It is most frequently administered in combination with fluorouracil and leucovorin for the treatment of colorectal cancer. Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin. 

In addition to the usual intravenous or oral routes, some anticancer agents have been administered by regional intraarterial perfusion to increase drug delivery to the tumor itself and at the same time diminish systemic toxicity. Thus, patients with metastatic carcinomas of the liver and little or no disease elsewhere (a common occurrence in colorectal cancer) can be treated with a continuous infusion of fluorouracil or floxuridine through a catheter implanted in the hepatic artery. 

Levamisole has been used successfully in treating chronic infections. It also has been approved for use in combination with fluorouracil in the treatment of colorectal cancer. 

C. Levy-Piedbois, I. Durand-Zaleski, H. Juhel, C. Schmitt, A. Bellanger, P. Piedbois, Cost-effectiveness of second-line treatment with irinotecan or infusional 5-fluorouracil in metastatic colorectal cancer, Ann. Oncol. 11 (2000) 157-161. 

Kidd EA, Yu J, Li X et al. Variance in the expression of 5-fluorouracil pathway genes in colorectal cancer. Clin Cancer Res 2005 11 2612-2619. 

Wang TL, Diaz LA, Jr., Romans K et al. Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients. Proc Natl AcadSci USA 2004 101 3089-3094. 

Colorectal cancer (CRC) is the third most common cause of cancer-related death in women and men in the United States. The current therapeutic options for patients with metastatic CRC (mCRC) are 5-fluorouracil (5-FU) based chemotherapy regimens with the addition of irinotecan (CPT-11) or oxaliplatin. It still remains a challenge for oncologists to evaluate the reasons for a wide variation in response and toxicity among patients undergoing systemic 5-FU based chemotherapy. Pharmacogenomics... 

Jemal A, Siegel R, Ward E et al. Cancer statistics, 2006. CA Cancer J Clin 2006 56 106-130. de Gramont A, Figer A, Seymour M et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000 18 2938-2947. 

Douillard JY, Cunningham D, Roth AD et al. Irinotecan combined with fluorouraeil eompared with fluorouracil alone as first-line treatment for metastatic colorectal cancer a multieentre randomised trial. Lancet 2000 355 1041-1047. 

Thirion P, Michiels S, Pignon JP et al. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer an updated meta-analysis. J Clin Oncol 2004 22 3766-3775. 

Sobrero AF, Aschele C, Bertino JR. Fluorouracil in colorectal cancer a tale of two drugs implieations for biochemical modulation. JClin Oncol 1997 15 368-381. 

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