European Georges Pompidou Hospital, Paris, France; René Descartes University, Paris V, France.
Jean Godinot Institute, Reims, France.
Eur J Cancer. 2018 Jul;97:41-48. doi: 10.1016/j.ejca.2018.03.008. Epub 2018 Apr 7.
Treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC.
Clinical data were collected retrospectively in 17 centres in Europe. Eligible patients had undergone rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT and CABA, in any order). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Data on toxicities were collected.
A total of 69 of 562 patients (Eastern Cooperative Oncology Group performance status 0-1 69%) were rechallenged with CABA (25 mg/m q3w, 58%; 20 mg/m q3w, 27.5%; other, 14.5%) for 1-10 (median 6) cycles; 76.8% received prophylactic granulocyte colony-stimulating factor. Median radiological or clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3-15.7) from the first CABA rechallenge cycle, 59.9 months (47.8-67.1) from the first life-extending therapy in mCRPC and 78.3 months (66.4-90.7) from mCRPC diagnosis. Best clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of prostate-specific antigen decreased by ≥ 50% in 24% of patients at rechallenge (71% with initial CABA). There was no grade ≥III peripheral neuropathy or nail disorders.
CABA rechallenge may be a treatment option without cumulative toxicity in heavily pretreated patients with mCRPC who are still fit and had a progression >3 months after the last CABA injections.
先前接受多西他赛（DOC）、卡巴他赛（CABA）和新激素治疗（NHT）治疗的转移性去势抵抗性前列腺癌（mCRPC）患者的治疗选择有限。由于累积毒性，重新使用 DOC 受到限制。本研究调查了 CABA 重用于 mCRPC 的疗效和安全性。
在欧洲的 17 个中心回顾性收集临床数据。符合条件的患者在三线治疗（DOC、NHT 和 CABA，顺序任意）后接受卡巴他赛重治。使用 Kaplan-Meier 法估计总生存期（OS）和无进展生存期（PFS）。收集毒性数据。
共有 562 例患者中的 69 例（东部肿瘤协作组体能状态 0-1 为 69%）接受 CABA 重治（25mg/m q3w，25%；20mg/m q3w，27.5%；其他，14.5%），治疗 1-10 个周期（中位数 6 个）；76.8%接受预防性粒细胞集落刺激因子治疗。初始 CABA 治疗时，CABA 重治的中位影像学或临床 PFS 为 7.8 个月，中位 OS 为 13.7 个月（95%置信区间 [CI]：9.3-15.7），从首次 CABA 重治周期开始，mCRPC 中首次延长生命治疗的中位 OS 为 59.9 个月（47.8-67.1），mCRPC 诊断的中位 OS 为 78.3 个月（66.4-90.7）。最佳临床获益为改善（34.3%）或稳定（47.8%）。17.9%的患者对重治无反应（初始 CABA 中为 3.1%）。24%的患者在重治时前列腺特异性抗原下降≥50%（初始 CABA 中为 71%）。无≥3 级周围神经病变或指甲疾病。
对于仍适合治疗且在最后一次 CABA 注射后 3 个月以上出现进展的，先前接受过多西他赛、卡巴他赛和新激素治疗的 mCRPC 重度预处理患者，CABA 重治可能是一种无累积毒性的治疗选择。
