Cabazitaxel Schedules in Metastatic Castration-Resistant Prostate Cancer: A Review

Abstract

Cabazitaxel (25 mg/m2 every 3 weeks) is the standard second-line chemotherapy for patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. It is associated with a risk of neutropenic complications, which may be a barrier to its use in daily clinical practice, particularly in frail elderly patients. Here the authors reviewed key studies conducted with cabazitaxel (TROPIC, PROSELICA, AFFINITY, CARD and the European compassionate use program) and pilot studies with adapted schedules. Based on this review, the use of prophylactic granulocyte colony-stimulating factor from cycle 1 appears crucial to maximize the benefit-risk ratio of cabazitaxel in metastatic castration-resistant prostate cancer. Preliminary data with alternative schedules look promising, especially for frail patients. Results of the ongoing Phase III CABASTY trial (ClinicalTrials.gov: NCT02961257 ) are awaited.

The emerging role of cross-resistance between taxanes and AR-targeting therapy in metastatic prostate cancer

“…32 The use of nanoparticles for docetaxel delivery has been proved to reduce docetaxel efflux and improve docetaxel sensitivity. 33 34 Another important mechanism for docetaxel resistance is the reactivation of AR activity. 32 It has been proved that AR gene alterations that render AR translocation independent of microtubule control may lead to docetaxel resistance.…”

“…35 For neutropenia, the application of prophylactic granulocyte colony-stimulating factor could maximise the benefit-risk ratio of cabazitaxel in mCRPC. 34 In addition, the combination with other cytotoxic chemotherapies could induce severe and potentially fatal complications, including fatal neutropenic enterocolitis. 36 Therefore, it is important to illustrate the mutual mechanism of different therapies to further avoid the accumulated drug toxicity and severe complications.…”

“…33 Clinically, cabazitaxel is the standard second-line chemotherapy for patients with mCRPC previously treated with docetaxel, which is supported by multiple clinical trials including TROPIC (XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer), PROSELICA (Cabazitaxel at 20 mg/m ² Compared to 25 mg/m ² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer) and AFFINITY (Comparison of Cabazitaxel/Prednisone Alone or in Combination With Custirsen for 2nd Line Chemotherapy in Prostate Cancer). 34 Another important mechanism for docetaxel resistance is the reactivation of AR activity. 32 It has been proved that AR gene alterations that render AR translocation independent of microtubule control may lead to docetaxel resistance.…”

L‐type amino acid transporter 1 inhibitor JPH203 prevents the growth of cabazitaxel‐resistant prostate cancer by inhibiting cyclin‐dependent kinase activity

“…Cabazitaxel is the standard chemotherapy for patients with metastatic castration-resistant prostate cancer (CRPC) after docetaxel. 2 While cabazitaxel has shown some efficacy, drug resistance remains a challenge as it eventually does occur, and when it does, there are no longer effective drugs for PC. 3 We previously cultured PC cells in medium containing cabazitaxel for an extended time and established a cabazitaxel-resistant cell line as a tool to search for effective drugs.…”

“…Metastatic PC is usually treated with androgen receptor (AR)‐axis‐targeted (ARAT) drugs that target AR; however, advanced cancers are treated with chemotherapy. Cabazitaxel is the standard chemotherapy for patients with metastatic castration‐resistant prostate cancer (CRPC) after docetaxel 2 . While cabazitaxel has shown some efficacy, drug resistance remains a challenge as it eventually does occur, and when it does, there are no longer effective drugs for PC 3 .…”