Oral fluoropyrimidines: a closer look at their toxicities.
Patient preferences, quality of life issues, and economic considerations are driving the development of orally administered chemotherapy. Oral fluorinated pyrimidines, which have been used in Japan, are attracting increasing interest as a means to provide convenient, less toxic treatment without compromising efficacy. The oral fluoropyrimidines provide prolonged 5-fluorouracil (5-FU) exposure at lower peak concentrations than those observed with bolus intravenous administration. Moreover, depending on the dose schedule, the pharmacokinetics of the oral fluoropyrimidines may mimic the pharmacokinetics of continuous-infusion 5-FU. This review focuses on the toxicity profiles of five emerging oral fluoropyrimidine antineoplastic drugs: combined uracil and tegafur (UFT), capecitabine, eniluracil, S-1, and emitefur (BOF-A2). Different patterns of toxicities emerge from an analysis of the clinical trials of these agents relative to 5-FU administered as an intermittent intravenous bolus or as continuous infusion. The results of ongoing phase III trials comparing the oral fluoropyrimidines with conventional regimens of 5-FU plus leucovorin and 5-FU by continuous intravenous infusion are necessary before their therapeutic role in the management of colorectal carcinoma can be defined.
Macdonald
J S
JS
Department of Medicine and Gastrointestinal Oncology Program, St. Vincents Comprehensive Cancer Center, New York, New York 10011-5201, USA.
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives; D006801:Humans; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005641:Tegafur; C073482:eniluracil; D014498:Uracil; D000069287:Capecitabine; D005472:Fluorouracil