Interferon alfa Fluorouracil

The UK manufacturers say that the maximum tolerated capecitabine dose when used alone is 3000 mg/m, but when combined with interferon alfa-2a (3 million units/m daily) the maximum tolerated dose is 2000 mg/m. Capecitabine is a prodrug of fluorouracil, which is thought to be modulated by interferon alfa. See also Fluorouracil + Interferon alfa , p.633. 

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. 

Initial studies have suggested that interferons may have synergistic activity with fluorouracil (144,145). Interferon alfa-2b has also been associated with an 80% increase in fluorouracil AUC (146). 

Wadler S, Lyver A, Wiernik PH. Clinical toxicities of the combination of 5-fluorouracil and recombinant interferon alfa-2a an unusual toxicity profile. Oncol Nurs Forum 1989 16(Suppl 6) 12-15. 

Wadler S, Wiemik PH. Clinical update on the role of fluorouracil and recombinant interferon alfa-2a in the treatment of colorectal carcinoma. Semin Oncol 1990 17(1 Suppl 1) 16-21. 

A 33-year-old man developed a delayed hemolytic reaction 7 days after red cell transfusion (224). Additional investigations showed the presence of an anti-M antibody, the production of which was supposedly caused by chemoimmunotherapy (interferon alfa, interleukin-2, and 5-fluorouracil) which was begun 24 hours after transfusion. 

Greco FA, Fighn R, York M, Einhom L, Schilsky R, Marshall EM, Buys SS, Froimtchuk MJ, Schuller J, Schuchter L, Buyse M, Ritter L, Man A, Yap AK. Fhase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer. J Clin Oncol 1996 14(10) 2674-81. 

Patt YZ, Hoque A, Lozano R, et al. Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin. J Clin Oncol 1997 15 1432-1438. 

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. 

Schuller J, Czejka MJ, Schernthaner G, Fogl U, Jager W, Micksche M. Influence of interferon alfa-2b with or without folinic acid on pharmacokinetics of fluorouracil. Semin Oncol (1992) 19 (2 suppl 3) 93-7,... 

Danhauser LL, Freimann JH, Gilchrist TL, Gutterman JU, Hunter CY, Yeomans AC, Markowitz AB. Phase I and plasma pharmacokinetic study of infusional fluorouracil combined with recombinant interferon alfa-2b in patients with advanced cancer. J Clin Oncol 0993) 11,751-61. 

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