Tanaka Nobumichi, Nishimura Kazuo, Okajima Eijiro, Ina Kenji, Ogawa Osamu, Nagata Hirohiko, Akakura Koichiro, Fujimoto Kiyohide, Gotoh Momokazu, Teramukai Satoshi, Hirao Yoshihiko
Nara Medical University, Department of Urology , Kashihara.
Osaka Medical Center for Cancer and Cardiovascular Diseases, Department of Urology, Osaka.
Jpn J Clin Oncol. 2017 Mar 1;47(3):247-251. doi: 10.1093/jjco/hyw193.
Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients.
This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/m2 of docetaxel, and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. Treatment was planned for 10 cycles, and continued for at least four cycles depending on the observation of PSA flare. The primary endpoint was PSA response defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints were safety, PSA flare, time to PSA failure and adherence rate to protocol treatment (10 cycles).
Between January 2011 and February 2014, a total of 76 chemotherapy-naïve CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%).
The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed.
此前，一项随机对照试验（TAX327）揭示了多西他赛联合泼尼松化疗的疗效。另一方面，多项研究表明，低剂量地塞米松可使去势抵抗性前列腺癌（CRPC）患者的前列腺特异性抗原（PSA）产生较高反应。本研究的目的是评估多西他赛联合地塞米松化疗在CRPC患者中的疗效和安全性。
本研究为单臂多机构II期试验。患者接受75mg/m²多西他赛治疗，并在整个治疗期间每天口服两次0.5mg地塞米松。计划进行10个周期的治疗，并根据PSA波动情况持续至少4个周期。主要终点为PSA反应，定义为从基线水平降低至少50%并持续至少3周。次要终点包括安全性、PSA波动、PSA失败时间以及方案治疗（10个周期）的依从率。
2011年1月至2014年2月，共纳入76例未接受过化疗的CRPC患者。75例患者接受了多西他赛联合地塞米松化疗。入组时的中位年龄和PSA水平分别为71岁（53 - 85岁）和23.2ng/mL（2.9 - 852）。PSA反应率为76.8%（90%置信区间（CI）：66.9 - 84.9）。所有患者中，30例患者完成了10个周期的化疗（40%）。PSA波动发生率为10.7%（8例患者）。PSA失败的中位时间为369天（95%CI：245 - 369）。最常观察到的不良事件是血液毒性（2级或更高级别的中性粒细胞减少：100%）。
本研究显示与既往报道相比，PSA反应显著较高。大多数患者对方案治疗耐受性良好，但经常观察到血液毒性。
