New approaches to the treatment of advanced breast cancer

The increase in our understanding of the mode of action of drugs and their potential interactions is allowing treatment strategies to be designed to optimize efficacy and minimize toxicity. Combination chemotherapy may entail the use of concurrent administration of two or more agents, or sequential or alternating administration of single agents or combinations. It is increasingly important to understand the advantages and disadvantages of each of these strategies, and the influence of each component of a combination therapy. Biochemical modulation is now used to enhance drug efficacy: the metabolism of 5-fluorouracil can be modified using leucovorin, methotrexate and 5-ethynyluracil; etoposide enhances the action of platinum drugs by inhibiting repair of the platinum-damaged DNA; and treatment with topoisomerase I inhibitors can increase sensitivity to topoisomerase II inhibitors. The role of docetaxel in combinations is now under investigation. Docetaxel (Taxotere) has the following features which indicate that it will be a useful drug in combination: the unique mechanism of action of the taxoids; neutropenia as the single dose-limiting toxicity; and a broad spectrum of antitumour activity. Clinical trials are ongoing to examine the use of docetaxel combination regimens in several disease areas.