Time to Progression and Safety Results of a Nonspecific Cytochrome-P 17 Inhibitor after Response/Stabilization to Docetaxel as a Maintenance Strategy in Metastatic Castratation-Resistant Prostate Cancer
ANNALS OF ONCOLOGY(2012)
摘要
ABSTRACT Background The first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) consists of docetaxel-based chemotherapy. The median time to progression (TTP) from chemotherapy initiation is 6-8 months (mo). Ketoconazole is a nonspecific cytochrome-P 17 inhibitor (CYP17i) that blocks adrenal androgen synthesis. Low-dose ketoconazole (LDK), (200 mg, t.d.s) has shown interesting activity in mCRPC after progression to androgen deprivation. The role of a CYP17i in the maintenance setting after response/stabilization to docetaxel has never been studied. Methods Thirty-eight mCRPC patients showing progression to luteinizing-hormone releasing hormone agonists (LHRHa), maintained LHRHa and received a median of 7 cycles of front-line three-weekly docetaxel (75 mg/m2) plus daily prednisone (10 mg). Twenty out of the thirty-eight patients showing no progression to docetaxel were enrolled. After docetaxel, ten patients were assigned to LDK maintenance treatment plus prednisone (10 mg/day) and LHRHa, and ten patients received LHRHa alone. TTP was the primary endpoint. Results After 33 months follow-up, a median TTP from docetaxel initiation was 11.5 months (IC95%: 6.3-16.6) for maintenance therapy and 9.2 months (IC95%: 8.5-9.9) for the control arm p = 0.047). Maintenance treatment was well tolerated with only one patient experiencing a grade 4 adverse event (non-symptomatic pulmonary embolism). Grade 1 and 2 asthenia and hot flashes worsening were the most common toxicities (table). Conclusions This is the first study testing a CYP17i for maintenance therapy after response/stabilization to docetaxel. A more than 2 months significant benefit in TTP with a favorable toxicity profile is observed. A further prospective analysis in a larger series using a CYP17i is warranted. Toxicity profile of maintenance therapy with a CYP17 inhibitor. Grade Toxicity 1 2 3 4 5 Asthenia 3 2 - - - Diarrhea 1 1 - - - Hepatotoxicity 1 1 - - - Hyporexia - 1 - - - Cephalea 1 - - - - Hot flashes 1 4 - - - Fluid Retention 1 2 - - - Pulmonary embolism - - - 1 - Disclosure All authors have declared no conflicts of interest.
更多查看译文
关键词
prostate cancer,docetaxel,inhibitor,castratation-resistant
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要