Theme Cancer, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Department of Hematalogy and Oncology, Stavanger University Hospital, PB 8100, 4068 Stavanger, Norway.
Eur J Cancer. 2018 Jul;97:33-40. doi: 10.1016/j.ejca.2018.03.007. Epub 2018 Apr 21.
Patients treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) may experience dose delays and reductions or terminate treatment because of toxicity. A lower and more frequent dose of cabazitaxel could improve dose intensity.
This prospective, multi-center, phase II study randomly assigned 101 patients to Arm A, cabazitaxel Q3W, 25 mg/m or Arm B, Q1W, 10 mg/m 5 of 6 weeks. The primary end-point was dose intensity, and we hypothesised that the experimental arm (Arm B) would result in a 20% absolute increase in the relative cumulative dose by week 18. Secondary end-points were overall survival (OS), progression-free survival (PFS), pain progression, radiological and prostate-specific antigen (PSA) response rates, quality of life (Functional Assessment of Cancer Therapy Prostate) and tolerability.
Median doses of cabazitaxel were 276 mg (45-320) and 257 mg (20-330) in Arms A and B, respectively, at week 18 (p = 0.13). More patients in Arm B stopped treatment because of toxicity. Median PFS in Arms A and B were 6.0 and 6.4 months (hazard ratio [HR] 0.73, 95% confidence interval [CI]: 0.47-1.13, p = 0.156) and for OS, 14.6 and 15.6 months (HR 0.95, CI: 0.58-1.58, p = 0.85), respectively. PSA responses ≥50% were seen in 52% and 46% of patients in Arms A and B, respectively. A higher incidence of febrile neutropenia was observed in the standard arm (10 events versus 1, p < 0.008). A grade V febrile neutropenia occurred in Arm A. Low-grade haematuria was more prevalent with weekly cabazitaxel (15 events versus 5, p = 0.003). Three patients in Arm B experienced clinically significant inflammation of the ureters. A toxicity is not previously described for cabazitaxel.
Weekly cabazitaxel reduces the incidence of febrile neutropenia but does not increase the dose intensity compared with the standard therapy. Cabazitaxel has clinical meaningful efficacy in heavily pre-treated patients with mCRPC.
接受卡巴他赛治疗转移性去势抵抗性前列腺癌（mCRPC）的患者可能因毒性而出现剂量延迟和减少或终止治疗。较低且更频繁的卡巴他赛剂量可能会提高剂量强度。
这是一项前瞻性、多中心、二期研究，将 101 名患者随机分为 A 组（卡巴他赛 Q3W，25mg/m 2 ）和 B 组（卡巴他赛 Q1W，10mg/m 2 ）。主要终点为剂量强度，我们假设实验组（B 组）将在第 18 周时使相对累积剂量绝对增加 20%。次要终点为总生存期（OS）、无进展生存期（PFS）、疼痛进展、影像学和前列腺特异性抗原（PSA）反应率、生活质量（癌症治疗功能评估前列腺）和耐受性。
第 18 周时，A 组和 B 组的卡巴他赛中位数剂量分别为 276mg（45-320）和 257mg（20-330）（p=0.13）。B 组更多的患者因毒性停止治疗。A 组和 B 组的中位 PFS 分别为 6.0 和 6.4 个月（风险比[HR]0.73，95%置信区间[CI]：0.47-1.13，p=0.156），OS 分别为 14.6 和 15.6 个月（HR 0.95，CI：0.58-1.58，p=0.85）。A 组和 B 组分别有 52%和 46%的患者 PSA 反应≥50%。标准组中发热性中性粒细胞减少症的发生率较高（10 例与 1 例，p<0.008）。A 组发生 1 例 5 级发热性中性粒细胞减少症。每周给予卡巴他赛时，血尿发生率较高（15 例与 5 例，p=0.003）。B 组有 3 例患者发生输尿管明显炎症。卡巴他赛的毒性以前没有被描述过。
与标准治疗相比，每周给予卡巴他赛可降低发热性中性粒细胞减少症的发生率，但不会增加剂量强度。卡巴他赛在经过大量预处理的 mCRPC 患者中具有明显的临床疗效。
