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.
Di Costanzo
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F
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
Sdrobolini
A
A
Gasperoni
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S
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