The role of cabazitaxel in the treatment of metastatic castration-resistant prostate cancer

Abstract

For decades, cytotoxic therapy was considered ineffective for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Earlier therapies such as estramustine and mitoxantrone received regulatory approval based upon improvement in palliative endpoints. In 2004, docetaxel became the first treatment to demonstrate a significant survival benefit in patients with mCRPC based on two randomized phase III studies, TAX327 and SWOG 99-16. Cabazitaxel, a third-generation taxane, was chosen for clinical development based on its decreased affinity for the drug efflux pump, p-glycoprotein, which is a frequent cause of drug resistance in docetaxel-resistant preclinical models. In 2010, cabazitaxel was approved by the US Food and Drug Administration as the first therapy to show a survival benefit for the treatment of patients with docetaxel-refractory mCRPC. This review summarizes the existing literature on the use of cabazitaxel, focusing on its efficacy and safety in combination with prednisone in the treatment of mCRPC, as well as its role in an era of new therapeutic options.

Perplexing Role of P-Glycoprotein in Tumor Microenvironment

“…Similarly, semisynthetic analogs of taxanes have been utilized in the development of several novel compounds with significantly higher efficiency against paclitaxel-resistant cancers. These include cabazitaxel (FDA approved) and ortataxel which have been shown to be efficient in hormone refractory metastatic prostrate cancer (81,82). Further, these compounds have been shown to be less amenable to efflux by P-gp.…”

Docetaxel–Cabazitaxel–Enzalutamide Versus Docetaxel–Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer

“…U nemocných léčených kabazitaxelem jsme vzhledem k jeho hematologické toxicitě aplikovali primární profylaxi pegfilgrastimem. Profylaktická aplikace růstových faktorů významně redukuje riziko vzniku neutropenie a její komplikaci (HR 0,7; p = 0,04) [16]. Mezi rizikové faktory vzniku neutropenie stupně 3-4 patří věk nad 75 let, aplikace prvního cyklu a počet neutrofilů méně než 4 000/ mm 3 před podáním kabazitaxelu [17].…”

Molecular Mechanisms of Therapies for Prostate Cancer with Bone Metastasis

“…Docetaxel used in combination with other therapies has provided some promising results of progression-free survival. 7,11,12 Even so, some PCa becomes resistant to docetaxel and new treatment options are needed. Cabazitaxel was approved by the U.S. Food and Drug Administration (FDA) to treat docetaxel-resistant PCa, and works by targeting microtubules, altering the efflux pump in the cell (so that drug remains in the cell longer), and inducing apoptosis.…”

“…Cabazitaxel was approved by the U.S. Food and Drug Administration (FDA) to treat docetaxel-resistant PCa, and works by targeting microtubules, altering the efflux pump in the cell (so that drug remains in the cell longer), and inducing apoptosis. 12 Carboplatin (a platinum-based drug), and everolimus (an mTOR inhibitor) have been used in clinical trials as a combination therapy and have been shown to exert antitumor effects and to reduce prostate-specific antigen (PSA) levels. 7 Chemotherapy agents such as docetaxel can be beneficial for many patients with metastatic CRPC; however, more specific bone-targeting agents could help eliminate the adverse effects to other non-cancerous replicating cells throughout the patient's body.…”