The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness.
Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel demonstrated linear pharmacokinetics and a terminal elimination half-life comparable to that of docetaxel, findings which support dosing as a single infusion in 3-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m2 every 3 weeks. Antitumor activity was demonstrated in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24%, and sustained tumor stabilizations were also observed. The TROPIC phase III study, performed in patients with metastatic, castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support.
Written by:
Mita AC, Figlin R, Mita MM. Are you the author?
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center.
Reference: Clin Cancer Res. 2012 Oct 22. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-12-1584
PubMed Abstract
PMID: 23091116
