Details

Autor(en) / Beteiligte

• de Morrée, Ellen
• van Soest, Robert
• Aghai, Ashraf
• de Ridder, Corrina
• de Bruijn, Peter
• Ghobadi Moghaddam-Helmantel, Inge
• Burger, Herman
• Mathijssen, Ron
• Wiemer, Erik
• de Wit, Ronald
• van Weerden, Wytske

Titel

Understanding taxanes in prostate cancer; importance of intratumoral drug accumulation

Ist Teil von

• The Prostate, 2016-07, Vol.76 (10), p.927-936

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• BACKGROUND Resistance to docetaxel is common in metastatic castration‐resistant prostate cancer (mCRPC) and may be caused by sub‐therapeutic intratumoral drug concentrations. Cabazitaxel demonstrated survival benefit in docetaxel‐pretreated and docetaxel‐refractory patients. In this study, we investigated whether the superior antitumor activity of cabazitaxel in mCRPC is explained by higher intratumoral cabazitaxel levels. Since recent studies suggest a reduced efficacy of docetaxel following treatment with novel androgen receptor (AR)‐targeted agents, we also investigated taxane efficacy in an enzalutamide‐resistant tumor model. METHODS Intratumoral concentrations of docetaxel and cabazitaxel were correlated with antitumor activity in docetaxel‐naïve, docetaxel‐resistant, and enzalutamide‐resistant patient‐derived xenografts (PDXs) of prostate cancer. RESULTS Intratumoral drug levels were negatively related to intrinsic and acquired resistance to docetaxel. Also, the observed stronger antitumor activity of cabazitaxel was associated with increased cumulative exposure and higher intratumoral of cabazitaxel concentrations in all PDXs. CONCLUSIONS The superior antitumor activity of cabazitaxel in docetaxel‐ and enzalutamide‐resistant tumors can be partly attributed to higher intratumoral drug concentrations. Especially for patients who are intrinsically resistant to docetaxel resulting from suboptimal intratumoral docetaxel concentrations, cabazitaxel may be the preferred chemotherapeutic agent. Prostate 76:927–936, 2016. © 2016 Wiley Periodicals, Inc.