Oral fluoropyrimidines among the new drugs for patients with metastatic breast cancer

• Published in: British journal of cancer Vol. 84; no. 11; pp. 1437 - 1442
• Main Author: LEONARD, R. C. F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.2001
• Subjects: Administration, Oral; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - pharmacology; Antineoplastic agents; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Capecitabine; Chemotherapy; Clinical Trials as Topic; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Drug Resistance, Neoplasm; Female; Fluorouracil - analogs & derivatives; Humans; Medical sciences; Pharmacology. Drug treatments; Review; Treatment Outcome; Antineoplastic agent; Human; Drug combination; Capecitabine; Treatment efficiency; Fluoropyrimidine derivatives; Oral administration; Review; Malignant tumor; Mammary gland diseases; Alkaloid; Chemotherapy; Limit dose; Treatment; Taxane derivatives; Phase II trial; Phase I trial; Pyrimidine derivatives; Advanced stage; Fluorine Organic compounds; Mammary gland; Antimitotic; Vinorelbine; Fluorouracil
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1054/bjoc.2001.1819

Although drugs such as the taxoids and vinorelbine have increased the options available for anthracycline-resistant metastatic breast cancer, new therapeutic options are needed, particularly for taxoid-refractory tumours. Increasing emphasis is being placed on the development of oral agents, which many patients prefer provided efficacy is not compromised, particularly if the oral agents are less toxic than current intravenous agents. Capecitabine, a new, oral fluoropyrimidine, mimics continuous infusion 5-FU and is activated preferentially at the tumour site. Phase II studies of capecitabine have demonstrated encouraging response rates in patients with few further treatment options (20% response with an additional 43% achieving stable disease in paclitaxel-refractory patients; 36% response with a further 23% achieving stable disease in anthracycline-refractory patients). In addition, a randomized, phase II trial demonstrated a response rate of 30% (95% Cl: 19-43%) with capecitabine as first-line treatment for metastatic breast cancer, compared with 16% (95% Cl: 5-33%) in patients receiving low-dose CMF. These trials also showed that capecitabine has a favourable safety profile typical of infused fluoropyrimidines. Both alopecia and myelosuppression were rare. Capecitabine may therefore provide an effective, well-tolerated and convenient alternative to intravenous cytotoxic agents, not only in taxoid-resistant patients, but also in anthracycline-resistant metastatic breast cancer or as first-line therapy. Furthermore, the low incidence of myelosuppression makes capecitabine an attractive agent for incorporation into combination regimens with agents such as epirubicin/doxorubicin, the taxoids and vinorelbine.