Docetaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of metastatic breast cancer

Abstract

Docetaxel is a member of the taxoid class of antineoplastic agents. Its mechanism of action is primarily related to its ability to enhance microtubule assembly and to stabilise microtubules by preventing their depolymerisation, thus disrupting normal cell division. Docetaxel has significant cytotoxic activity against human breast cancer cell lines and freshly explanted human breast cancer cells in vitro. It has also shown activity in mice against mammary tumours and human mammary tumour xenografts. Docetaxel has been investigated in the treatment of patients with advanced and/or metastatic breast cancer in European and North American phase II trials using an initial dose of 100 mg/m2 infused over 1 hour every 3 weeks. As first-line treatment, monotherapy with docetaxel was associated with complete and partial response rates of 5 to 16% and 49 to 53%, respectively, with an overall (complete plus partial) response rate of 54 to 68%. The median overall survival time of patients in one study was > or = 71 weeks. Docetaxel monotherapy has shown impressive activity as second-line therapy in patients with metastatic breast cancer who had relapsed while receiving adjuvant therapy or who had progressive disease following previous treatment, with overall response rates of 53 and 58% reported in 2 studies. A number of issues need to be addressed before the ultimate place of docetaxel in the management of metastatic breast cancer is fully established. The efficacy of docetaxel compared with standard agents and in combination regimens and its effect on quality-of-life aspects require further evaluation. Nevertheless, docetaxel is a promising new agent which has produced impressive clinical results and should be considered an alternative second-line treatment of patients with metastatic breast cancer.