Evaluation of the response to cabazitaxel of a docetaxel-responsive hormone-refractory prostate tumor xenograft model (HID28).

e15161 Background: Docetaxel was the first cytotoxic treatment demonstrating a survival benefit in metastatic castration-resistant prostate cancer (mCRPC) patients. Recently, cabazitaxel (a novel taxane) and abiraterone acetate (specific inhibitor of CYP17) have demonstrated a significant survival benefit in mCRPC patients progressing after receiving a docetaxel – containing regimen. Here we compare the antitumor efficacy of docetaxel, cabazitaxel and abiraterone acetate in the HID28 hormone-refractory human prostate carcinoma xenograft. Methods: HID28 tumor bearing nude mice received 20 mg/kg of docetaxel (IP, q3wk x 2), cabazitaxel at 15 and 20 mg/kg (IP, q3wk x 2) and abiraterone acetate at 50 mg/kg (PO, qdx21). Median tumor growth inhibition (T/C%) was evaluated as well as time course androgen receptor expression (4, 8 and 24h post dosing) by western blot analysis. Results: Docetaxel (20 mg/kg) inhibited tumor growth with a T/C%= 16.7% at D35, 2 partial (PR) and 1 complete (CR) tumor regressions, and with relapse of all tumors (6/6) observed at D42. Cabazitaxel demonstrated dose-dependent efficacy at D35 with T/C%= 10.8% and 1.4% for 15 and 20 mg/kg doses respectively. At a cabazitaxel dose of 15 mg/kg, 4/10 PR and 3/10 CR were observed, whereas 4/10 PR and 6/10 CR were observed at 20 mg/kg. At D42, 6/6 tumor relapses were observed at 15 mg/kg; whereas, only 3/6 relapses were observed at 20 mg/kg. No anti-tumor activity was demonstrated with abiraterone acetate as well as no significant decreases in testosterone levels compared to the vehicle group. Tolerability was good for all treatment groups, with a transitory maximum mean body weight loss of 12%, 6 days after treatments. Androgen receptor western blot expression analysis after 4, 8 and 24h post dosing demonstrated no significant difference between groups and over time. Conclusions: Cabazitaxel and docetaxel showed similar tolerability at equivalent dose levels. Cabazitaxel demonstrated superior antitumor efficacy over docetaxel at equivalent dosing in the HID28 hormone-refractory tumor model. These results support the clinical development of cabazitaxel in first line treatment of mCRPC patients.