Docetaxel: an alternative taxane in ovarian cancer.

Abstract

The taxanes paclitaxel and docetaxel are potent chemotherapeutic agents that block tubulin depolymerisation, leading to the inhibition of microtubule dynamics and cell cycle arrest. Although docetaxel and paclitaxel share a mutual tubulin binding site, mechanistic and pharmacological differences exist between these agents. For example, docetaxel has increased potency and an improved therapeutic index compared with paclitaxel, and its short 1-h infusion offers a substantial clinical advantage over the prolonged infusion durations required with paclitaxel. In clinical studies, docetaxel monotherapy demonstrated good response rates and an acceptable toxicity profile in both paclitaxel- and platinum-refractory ovarian cancer patients. In particular, neurotoxicity — a dominant side effect with both paclitaxel and cisplatin — occurs at a low incidence with docetaxel, making docetaxel a promising agent for combining cisplatin and other platinum compounds. In Phase II studies, the combination of docetaxel with either cisplatin or carboplatin has yielded impressive response rates of 69–74 and 81–87%, respectively. Furthermore, Phase III data suggest that docetaxel–carboplatin and paclitaxel–carboplatin are similarly efficacious with respect to progression-free survival and clinical response, although neurotoxicity occurs more frequently with the paclitaxel regimen. While paclitaxel–carboplatin remains the standard treatment for the management of advanced ovarian cancer, docetaxel–carboplatin appears to be a promising alternative, particularly in terms of minimising the incidence and severity of peripheral neuropathy.