Capecitabine, a new oral fluoropyrimidine for the treatment of colorectal cancer.
Capecitabine (Xeloda)(R) was developed as a tumour-selective fluoropyrimidine carbamate to achieve higher intratumoural 5-FU level and lower toxicity than 5-FU. Capecitabine passes unchanged through the gastrointestinal tract and is metabolised in the liver to 5'-deoxy-5-fluorocytidine (5'-DFCR). Here it is converted to doxifluridine (5'-DFUR) and finally, 5'-DFUR is metabolised by thymidine phosphorilase to 5-FU at the tumour site. Preclinical studies have demonstrated capecitabine's activity in both 5-FU-sensitive and 5-FU-resistant tumours. In a randomised phase II trial in advanced colorectal cancer the recommended dose and schedule of Capecitabine is 2.510 mg/m(2)/day (total dose divided into two equal morning and evening doses) given in an intermittent schedule (2 weeks on/1 week off). Phase III trials in patients with advanced colorectal cancer show a better response rate than the Mayo Clinic schedule, with no differences in terms of DR, PFS. Diarrhoea and hand-foot syndrome were the principal grade 3/4 toxicities noted, occurring in 10% and 16% of patients, respectively. The selectivity of this drug opens an important prospective in the treatment of colorectal cancer in advanced and adjuvant setting.
Dipartimento di Medicina Interna ed Oncologia Medica, Unità Operativa di Chemioterapia e Terapia Locoregionale dei Tumouri, Azienda Ospedaliera S. Maria, Terni, Italy. dicostanzo@sirio-oncology.it
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D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D011355:Prodrugs; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil