Buonerba Carlo, Sonpavde Guru, Vitrone Francesca, Bosso Davide, Puglia Livio, Izzo Michela, Iaccarino Simona, Scafuri Luca, Muratore Margherita, Foschini Francesca, Mucci Brigitta, Tortora Vincenzo, Pagliuca Martina, Ribera Dario, Riccio Vittorio, Morra Rocco, Mosca Mirta, Cesarano Nicola, Di Costanzo Ileana, De Placido Sabino, Di Lorenzo Giuseppe
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy.
J Cancer. 2017 Aug 22;8(14):2663-2668. doi: 10.7150/jca.20040. eCollection 2017.
Cabazitaxel is a second-generation taxane that is approved for use with concomitant low dose daily prednisone in metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure. Since the role of daily corticosteroids in improving cabazitaxel efficacy or ameliorating its safety profile has not been adequately investigated so far, we compared outcomes of patients receiving cabazitaxel with or without daily corticosteroids in a retrospective single-Institution cohort of mCRPC patients. Medical records of deceased patients with documented mCRPC treated with cabazitaxel following prior docetaxel between January, 2011 and January, 2017 were reviewed at the single participating center. Patients who were receiving daily doses of systemic corticosteroids other than low dose daily prednisone or prednisolone (<= 10 mg a day) were excluded. The primary end point of this analysis was overall survival (OS). Secondary end-points were exposure to cabazitaxel as well as incidence of grade 3-4 adverse events. Univariable and multivariable Cox proportional hazards regression was used to evaluate prednisone use and other variables as potentially prognostic for overall survival. Overall, among 91 patients, 57 patients received cabazitaxel concurrently with low dose prednisone and 34 patients did not receive concurrent prednisone. The median overall survival of the population was 9.8 months (interquartile range, 9 to 14). Patients receiving prednisone had an overall survival of 9 months (interquartile range, 8 to 12) vs.14 months (interquartile range, 9.4 to 16.7) for patients not treated with prednisone. Approximately 45% of patients had a >30% PSA decline at 12 weeks. Prednisone use was not significantly prognostic for overall survival or PSA decline ≥30% rates on regression analyses. Importantly, a >30% PSA decline at 12, but not at 3, 6, 9 weeks, was prognostic for improved survival at multivariate analysis The data presented here support the hypothesis that omitting daily corticosteroids in cabazitaxel-treated patients has no negative impact on either survival or safety profile. In the large prospective trial CABACARE, cabazitaxel-treated patients will be randomized to receive or not receive daily prednisone. The CABACARE (EudraCT n. 2016-003646-81) study is currently ongoing at University Federico II of Naples and at other multiple participating centers in Italy.
卡巴他赛是一种第二代紫杉烷类药物，被批准与低剂量每日一次的泼尼松联合用于多西他赛治疗失败后的转移性去势抵抗性前列腺癌（mCRPC）。由于目前尚未充分研究每日使用皮质类固醇在提高卡巴他赛疗效或改善其安全性方面的作用，我们在一个回顾性单机构队列的mCRPC患者中比较了接受或未接受每日皮质类固醇治疗的卡巴他赛患者的结局。在单个参与中心回顾了2011年1月至2017年1月期间接受卡巴他赛治疗且之前接受过多西他赛治疗并有记录的mCRPC死亡患者的病历。排除正在接受除低剂量每日一次的泼尼松或泼尼松龙（≤10毫克/天）以外的全身性皮质类固醇每日剂量治疗的患者。该分析的主要终点是总生存期（OS）。次要终点是卡巴他赛的暴露情况以及3-4级不良事件的发生率。使用单变量和多变量Cox比例风险回归来评估泼尼松的使用以及其他变量对总生存期的潜在预后价值。总体而言，在91例患者中，57例患者在接受卡巴他赛治疗的同时接受低剂量泼尼松治疗，34例患者未接受同时使用泼尼松治疗。该人群的中位总生存期为9.8个月（四分位间距，9至14个月）。接受泼尼松治疗的患者总生存期为9个月（四分位间距，8至12个月），而未接受泼尼松治疗的患者为14个月（四分位间距，9.4至16.7个月）。约45%的患者在12周时前列腺特异性抗原（PSA）下降>30%。回归分析显示，泼尼松的使用对总生存期或PSA下降≥30%的发生率没有显著的预后价值。重要的是，在多变量分析中，12周时PSA下降>30%可预测生存期改善，但3、6、9周时PSA下降>30%则无此作用。此处呈现的数据支持以下假设：在接受卡巴他赛治疗的患者中省略每日皮质类固醇对生存期或安全性均无负面影响。在大型前瞻性试验CABACARE中，接受卡巴他赛治疗的患者将被随机分组，分别接受或不接受每日泼尼松治疗。CABACARE（欧盟临床试验编号2016-003646-81）研究目前正在那不勒斯费德里科二世大学及意大利其他多个参与中心进行。
