Fluorouracil Folinates

Colorettai S-fluorouracil folinic add Irinotecan 5-fluorouracil/folinic acid Oxaliplatin + S-fluorouracil folinic acid... 

Myelosuppression caused by oxaliplatin is generally mild. Grade 3/4 anemia, neutropenia, and thrombocytopenia are observed in only 2-3% of patients. In combination with fluorouracil/folinic acid, the frequency is slightly higher, depending on the dose of fluorouracil (8,9). 

FOLFIRI Irinotecan 1 80 mg/m2 IV day 1 Folinic acid (leucovorin) 200 mg/m2 IV day 1 5-Fluorouracil 400-500 mg/m2 IV bolus, after folinic acid then 2400-3000 mg/m2 of 5-fluorouracil IV over 46 hours Repeat every 14 days... 

FOLFIRI Folinic acid (leucovorin) + 5-fluorouracil + Irinotecan given as combined IV boluses and continuous infusions... 

FOLFIRI folinic acid, fluorouracil, and infusional irinotecan... 

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. 

Fluorouracil 400 mg/m2 IV bolus, after folinic acid then 600 mg/m2 CIV over 22 hours days 1 and 2... 

International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol 1999 17 1356-1363. 

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. 

Metzger, G., Massari, C., Etienne, M.C., Comisso, M., Brienza, S., Touitou, Y., Milano, G., Bastian, G., Misset, J.L., Levi, F. Spontaneous or imposed circadian changes in plasma concentrations of 5-fluorouracil coadministered with folinic acid and oxaliplatin relationship with mucosal toxicity in patients with cancer. Clin. Pharmacol. Ther. 1994, 56 190-201. 

Levi, F., Zidani, R., Vannetzel, J.M., Per-point, B., Focan, C., Faggiuolo, R., Chollet, P., Garufi, C., Itzhaki, M., Dogliotti L. Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases a randomized multi-institutional trial. J. Natl Cancer Inst. 1994, 86 1608-1617. 

Howell, J.D., Warren, H.W., Anderson, XH., Kerr, D.X, McArdle, C.S. Intra-arterial 5-fluorouracil and intravenous folinic acid in the treatment of liver metastases from colorectal cancer. Eur. X Surg. 1999 165 652-658... 

Colitis has been reported as a rare comphcation of fluorouracil treatment. Two cases have been reported after intra-arterial chemotherapy (96). A fnrther case has been reported, described by the authors as neutropenic enterocolitis, presenting as abdominal pain, diarrhea, and neutropenia (97). Proven pseudomembranons colitis followed 36 weekly doses of fluorouracil (700 mg) and folinic acid (150 mg) the anthors believed that this was only the second reported case (98). 

Mortimer JE, Higano C. Continuous infusion 5-fluorouracil and folinic acid in disseminated colorectal cancer. Cancer Invest 1988 6(2) 129-32. 

An 80-year-old woman had a colonic resection for Duke s C stage adenocarcinoma and was then given fluorouracil 400 mg/m /day and folinic acid 200 mg/m /day for 5 days every 4 weeks. She later developed metastases and a second course of chemotherapy included irinotecan (180 mg/m ), fluorouracil 400 mg/m, followed by a continuous infusion of 2400 mg/m over 2 days, folinic acid 200 mg/m, ondansetron, and atropine. During the first course of chemotherapy she developed urticaria following the administration of ondansetron and folinic acid. The ondansetron was withdrawn and replaced by metoclopramide and prednisone. During the next course, just after the administration of folinic acid, metoclopramide, and prednisone, she had more urticaria and profound hjrpotension and required intravenous adrena-hne. Folinic acid was withdrawn and subsequent courses were uneventful... 

Fluorouracil (370 mg/m ) plus high-dose (175 mg) or low-dose (25 mg) folinic acid and either active or placebo levamisole has been evaluated in 4927 patients with colorectal cancer (23). Levamisole produced a significant excess of adverse dermatological events. Serious unexpected adverse events were rare. The authors concluded that the inclusion of levamisole in chemotherapy regimens for colorectal cancer does not delay recurrence or improve survival. 

Oxahplatin belongs to the group of diaminocyclohexane (DACH) platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid (8,9). 

If irinotecan is combined with 5-fluorouracil and calcium folinate, an infusion regimen of fluorouracil rather than bolus administration is associated with a lower incidence of severe toxicity (leukopenia and life-threatening sepsis) (157). 

Folic acid is a nutritional supplement frequently used during periods of deficiency. Folic acid needs increase during chronic diseases, such as malabsorption liver disease, alcoholism, and anticonvulsant or oral contraceptive use. Folic acid supplementation during pregnancy is strongly recommended to prevent neural tube defects to the unborn child. The active form of folic acid, folinic acid, is used in the management of certain medical diseases (e.g., patients taking methotrexate, and 5-fluorouracil). 

Saini A, Norman AR, Cunningham D, et al. Twelve weeks of protracted venous infusion of fluorouracil (5-FU) is as effective as 6 months of bolus 5-FU and folinic acid as adjuvant treatment in colorectal cancer. Br J Cancer 2003 88 1859-1865. 

Punt CJ, Nagy A, Douillard JY, et al. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer A randomised study. Lancet 2002 360 671-677. 

S.J., Brady, F., Jones, T, and Price, P.M. Tumor, normal tissue, and plasma pharmacokinetic studies of fluorouracil biomodulation with N-phosphonacetyl-L-aspartate, folinic acid, and interferon alfa. J. Clin. Oncol., 17 1580-1588, 1999. 

Fluorouracil is used to treat gastrointestinal and breast cancers, often together with synthetic folinates. 

Tsavaris N, Bacoyannis C, Milonakis N, Sarafidou M, Zamanis N, K goulas D, Kosmidis P. Folinic acid plus high-dose 5-fluorouracil witii allopurinol protection in the treatment of advanced colorectal carcinoma. EurJ Cancer (1990) 26,1054-6. 

---