Molecular basis for the development of novel taxanes in the treatment of metastatic breast cancer

Abstract

The identification of taxanes proved to be a significant advance in the treatment of breast cancer. First-generation taxanes achieved 35% to 55% response rates for women not previously treated with anthracyclines and exceeded 20% for anthracycline-resistant disease. Consequently, taxanes were established as a standard of care in metastatic disease. Subsequent research evaluated taxane monotherapy and combination therapy with other cytotoxic agents, as well as optimal dose and administration schedules to maximize efficacy while minimizing toxicities. Clinical trials suggested the optimal administration schedule and dose for paclitaxel was 80 mg/m 2 weekly, and this weekly schedule is commonly used. However, the solvents required for administration of first-generation taxanes are associated with significant toxicities and undermined clinical efficacy. These factors motivated development of taxane formulations that would enhance the therapeutic index and minimize toxicities. This article reviews the rationale for development of novel taxane formulations and emerging research regarding new formulations including oral taxanes, paclitaxel poliglumex, and vitamin E-based paclitaxel emulsion.