Di Lorenzo Giuseppe, Bracarda Sergio, Gasparro Donatello, Gernone Angela, Messina Caterina, Zagonel Vittorina, Puglia Livio, Bosso Davide, Dondi Davide, Sonpavde Guru, Lucarelli Giuseppe, De Placido Sabino, Buonerba Carlo
From the Department of Clinical Medicine, Federico II University, Naples (GDL, LP, DB, SDP, CB); Department of Oncology, Medical Oncology Unit, San Donato Hospital, Arezzo (SB); Department of Oncohematology, University Hospital of Parma, Parma (DG); Policlinico Hospital, Bari (AG); Ospedale Papa Giovanni Paolo XXIII Hospital, Bergamo (CM); Medical Oncology Unit, Istituto Oncologico Veneto-IRCCS, Padua (VZ); Medical Affairs Oncology Division, Sanofi, Milan, Italy (DD); Department of Medicine, Urologic Oncology, Division of Hematology & Oncology, University of Alabama at Birmingham, Birmingham, AL (GS); and Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy (GL).
Medicine (Baltimore). 2016 Jan;95(2):e2299. doi: 10.1097/MD.0000000000002299.
Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3-4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed "per cycle" incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel.The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis."Per cycle" incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86-0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34-0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86-1; P = 0.07). Patients with a body surface area >2 m2 presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86-1; P = 0.07), but decreased odds of having G3 to 4 anemia.Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment.
与米托蒽醌相比，卡巴他赛为多西他赛难治性去势抵抗性前列腺癌患者提供了生存优势。在激素难治性转移性前列腺癌卡巴他赛联合泼尼松与米托蒽醌联合泼尼松对比研究（TROPIC）试验中，3至4级（G3-4）中性粒细胞减少和发热性中性粒细胞减少相对常见，但在扩大使用计划（EAP）中其发生率较低。虽然多西他赛的累积剂量与神经病变有关，但卡巴他赛累积剂量的影响尚不清楚。在这项对前瞻性收集数据的回顾性分析中，作者评估了EAP意大利队列中“每周期”毒性的发生率及其预测因素，重点关注卡巴他赛累积剂量所产生的影响。
研究人群包括218名参加卡巴他赛EAP的意大利患者。在单变量和多变量分析中，使用广义估计方程模型评估选定变量对已确定的最相关不良事件的影响。G3至4级中性粒细胞减少的“每周期”发生率为8.7%，而发热性中性粒细胞减少在0.9%的周期中出现。所有发热性中性粒细胞减少事件均发生在前3个周期内。多变量逻辑回归分析显示，较高的卡巴他赛既往剂量与发生G3至4级中性粒细胞减少（比值比[OR]=0.90；95%置信区间[CI]：0.86-0.93；P<0.01）、发热性中性粒细胞减少（OR=0.52；95%CI：0.34-0.81；P<0.01）和G3至4级贫血（OR=0.93；95%CI：0.86-1；P=0.07）的几率降低相关。体表面积>2 m2的患者发生G3至4级中性粒细胞减少的几率增加（OR=0.93；95%CI：0.86-1；P=0.07），但发生G3至4级贫血的几率降低。
在评估的毒性中，作者未发现任何似乎与更高的卡巴他赛给药周期数相关的毒性。既往累积剂量与G3至4级中性粒细胞减少和贫血的减少相关。与较高剂量卡巴他赛相关的明显保护作用可能会受到早期剂量减少和早期与毒性相关的治疗中断的影响。由于该分析受其回顾性设计的限制，需要进行前瞻性试验来评估卡巴他赛治疗的最佳持续时间。
