Fluorouracil metastatic

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... 

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. 

Fluorouracil (5-FU)/ leucovorin (Mayo)- metastatic 5-FU 425 mg/M2 Leucovorin 20 mg/M2 REF Buroker et al. J Clin Oncol 1994 Repeat every 28-35 days IV bolus IV bolus 12 14-20 days 1 -5 days 1 -5... 

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. 

Mahjoubi M, Sadek H, Francois E, et al. Epidermoid anal canal carcinoma (EACC) activity of cisplatin and continuous 5 -fluorouracil in metastatic and/or local recurrent disease. Proc Annu Meet Am Soc Clin Oncol 1990 9 114. 

Schrijvers D, Johnson J, Jiminez U, et al. Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group. J Clin Oncol 1998 16 1054-1059. 

Murphy B, Li Y, Celia D, et al. Phase III study comparing cisplatin (C) and 5-Fluorouracil (F) versus cisplatin and paclitaxel (T) in metastatic/recurrent head and neck cancer (MHNC). ProcAnnu Meet Am Soc Clin Oncol 2001 20 A894. 

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. 

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. 

T. Leong, D. Lim-Joon, J. Mackay, D. Rischin, Oxaliplatin combined with infusional 5-fluorouracil and concomitant radiotherapy in inoperable and metastatic rectal cancer A phase I trial, Br. J. Cancer 92(4) (2005) 655-661. 

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. 

Thymidylate synthase protein expression in the primary tumor is not a useful predictor for either thymidylate synthase protein expression or response to 5-fluorouracil therapy in metastatic disease (52,53). Similarly, concordance rates for expression of HER family members ranges from 79% to 56% between primary breast cancer and matched distant... 

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... 

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. 

Van Cutsem E, Twelves C, Cassidy J et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer results of a large phase III study. J Clin Onco/2001 19 4097 106. 

Etienne MC, Chazal M, Laurent-Puig P et al. Prognostic value of tumoral thymidylate synthase and p53 in metastatic colorectal cancer patients receiving fluorouracil-based chemotherapy phenotypic and genotypic analyses. JC/iw Oncol 2002 20 2832-2843. 

Irinotecan is a prodrug that is converted mainly in the liver by the carboxylesterase enzyme to the SN-38 metabolite, which is 1000-fold more potent as an inhibitor of topoisomerase I than the parent compound. In contrast to topotecan, irinotecan and SN-38 are mainly eliminated in bile and feces, and dose reduction is required in the setting of liver dysfunction. Irinotecan was originally approved as second-line monotherapy in patients with metastatic colorectal cancer who had failed fluorouracil-based therapy. It is now approved as first-line therapy when used in combination with 5-FU and leucovorin. Myelosuppression and diarrhea are the two most common adverse events. There are two forms of diarrhea an early form that occurs within 24 hours after administration and is thought to be a cholinergic event effectively treated with atropine, and a late form that usually occurs 2-10 days after treatment. The late diarrhea can be severe, leading to significant electrolyte imbalance and dehydration in some cases. 

Advantage is taken of the properties of antimctabolitcs in chemotherapy. In cancer chemotherapy, several antimetabolites are used. These include methotrexate, 6-mercaptopunne, 6-thioguanine, 5-fluorouracil, and cystine arabinoside. In the chemotherapy of metastatic breast cancer, 5-fluorouracil and methotrexate, in combination with cyclophosphamide, have been used. Antimetabolites, sometimes along with corticosteroids, are used in the therapy of various autoimmune diseases, such as thrombocytenic purpura, thyroiditis, Goodpasture s syndrome, among others. 

Oxaliplatin is a third generation diaminocyclohexane platinum analog. Its mechanism of action is identical to that of cisplatin and carboplatin. However, it is not cross-resistant to cancer cells that are resistant to cisplatin or carboplatin on the basis of mismatch repair defects. This agent was recently approved for use as second-line therapy in metastatic colorectal cancer following treatment with the combination of fluorouracil-leucovorin and irinotecan, and it is now widely used as first-line therapy of this disease as well. Neurotoxicity is dose-limiting and characterized by a peripheral sensory neuropathy, often triggered or worsened upon exposure to cold. While this neurotoxicity is cumulative, it tends to be reversible—in contrast to cisplatin-induced neurotoxicity. 

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