title: Pharmacology and therapeutic efficacy of capecitabine: focus on breast and colorectal cancer.
abstract: Capecitabine (N -pentyloxycarbonyl-5-deoxy-5-fluorocytidine), an oral prodrug of 5-fluorouracil, has provided compelling efficacy data for the treatment of metastatic breast cancer and stage III or IV colorectal cancer, both as monotherapy and in combination regimens. The preferential conversion of capecitabine to 5-fluorouracil in neoplastic tissues renders this fluoropyrimidine particularly appealing for clinical use. The enzyme thymidine phosphorylase, which mediates the final step of the capecitabine activation pathway, is expressed in higher concentration in neoplastic than in healthy tissues. This makes capecitabine more tumor specific than other chemotherapeutic agents. Accordingly, capecitabine is generally well tolerated. In particular, the incidence of myelosuppression and alopecia is low, and the most common side effects, hand-foot syndrome and diarrhea, are usually manageable. Given its good toxicity profile, capecitabine was assessed in combination with several chemotherapeutic or biologic agents. In addition, the observation that thymidine phosphorylase is upregulated after treatment with other anticancer drugs, namely taxanes, provided a rationale for the prominent antitumor activity recently observed for the combination of capecitabine with these agents. This review provides an evidence-based update of clinical trials investigating the role of capecitabine in the treatment of breast and colorectal cancer, with special emphasis on pharmacological and safety issues that form the basis of currently used schedules.
authors.affiliation: Department of Oncology, University Hospital of Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.forename: Micol
authors.initials: M
authors.lastname: Mazzer
authors.forename: Stefano
authors.initials: S
authors.lastname: Moroso
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009362:Neoplasm Metastasis; D011355:Prodrugs
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil