Department of Urology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
BMC Cancer. 2020 Jul 13;20(1):649. doi: 10.1186/s12885-020-07131-6.
The recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m in Japan and Europe. Although lower doses are established alternatives based on randomized controlled trials, the safety and efficacy of 25 and 20 mg/m in real-world settings are not well established. Therefore, we investigated the safety and efficacy of cabazitaxel at the recommended starting dose or a lower dose (20 mg/m) in real-world clinical practice.
We compared the safety and efficacy of cabazitaxel between patients who received cabazitaxel at starting doses of 25 and 20 mg/m (C25 and C20, respectively) in a Japanese post-marketing surveillance study of 662 patients with docetaxel-refractory CRPC. Safety was assessed in terms of adverse drug reactions (ADRs). Prostate-specific antigen (PSA) response rate, overall survival (OS), and time-to-treatment failure (TTF) were compared between the C25 and C20 groups in unmatched patients and after applying propensity score matching.
The C20 and C25 groups comprised 190 and 159 patients without matching and 112 patients per group after matching. In unmatched patients, any-grade (C25 vs C20: 89.3% vs 78.4%, Fisher's p < 0.01) and grade ≥ 3 (81.1% vs 61.1%) ADRs were more frequent in the C25 group. Neutropenia (any grade: 61.6% vs 54.2%; grade ≥ 3: 55.3% vs 42.6%) and febrile neutropenia (grade ≥ 3: 30.2% vs 14.7%) were more frequent in the C25 group. In matched patients, the PSA response rate (reduction in PSA ≥30% from a baseline ≥5 ng/mL) was 26.4 and 32.0% in the C20 and C25 groups, respectively, median OS was 291 days (95% CI 230-not reached) versus not reached (hazard ratio 0.73, 95% CI 0.50-1.08), and TTF favored C25 (hazard ratio 0.75, 95% CI 0.57-0.99).
Clinicians should consider the patient's risk of clinically significant ADRs and prophylactic granulocyte colony stimulating factor when selecting the starting dose of cabazitaxel for CRPC. Some patients at high risk of ADRs or unfit patients may benefit from a lower starting dose of 20 mg/m, whereas fit patients may be candidates for a starting dose of 25 mg/m.
Not applicable.
在日本和欧洲，卡巴他赛治疗去势抵抗性前列腺癌（CRPC）的推荐起始剂量为 25mg/m2。虽然基于随机对照试验已确定较低剂量为替代方案，但在真实世界环境中，25 和 20mg/m2 的安全性和疗效尚未得到充分证实。因此，我们研究了在真实世界临床实践中使用推荐起始剂量或较低剂量（20mg/m2）的卡巴他赛的安全性和疗效。
我们比较了 662 例多西他赛难治性 CRPC 患者在日本上市后监测研究中接受卡巴他赛起始剂量为 25 和 20mg/m2（分别为 C25 和 C20）的患者之间的安全性和疗效。安全性根据药物不良反应（ADR）进行评估。在未匹配的患者和应用倾向评分匹配后，比较 C25 和 C20 组之间前列腺特异性抗原（PSA）反应率、总生存期（OS）和治疗失败时间（TTF）。
C20 和 C25 组分别包括 190 例和 159 例未匹配的患者和每组 112 例匹配的患者。在未匹配的患者中，C25 组任何等级（C25 比 C20：89.3%比 78.4%，Fisher's p<0.01）和≥3 级（C25 比 C20：81.1%比 61.1%）ADR 更为常见。中性粒细胞减少症（任何等级：61.6%比 54.2%；≥3 级：55.3%比 42.6%）和发热性中性粒细胞减少症（≥3 级：30.2%比 14.7%）在 C25 组更为常见。在匹配的患者中，C20 和 C25 组 PSA 反应率（基线 PSA≥5ng/ml 的 PSA 降低≥30%）分别为 26.4%和 32.0%，中位 OS 分别为 291 天（95%CI 230-未达到）和未达到（风险比 0.73，95%CI 0.50-1.08），TTF 有利于 C25（风险比 0.75，95%CI 0.57-0.99）。
临床医生在选择卡巴他赛治疗 CRPC 的起始剂量时，应考虑患者发生有临床意义的 ADR 的风险和预防性粒细胞集落刺激因子。某些 ADR 风险较高或不适合的患者可能受益于较低的起始剂量 20mg/m2，而适合的患者可能适合起始剂量 25mg/m2。
不适用。
