Zhang Yan, Mei Qian, Liu Yang, Li Xiang, Brock Malcolm V, Chen Meixia, Dong Liang, Shi Lu, Wang Yao, Guo Mingzhou, Nie Jing, Han Weidong
Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China.
Department of Surgery, Johns Hopkins University, Baltimore, MD, USA.
Oncoimmunology. 2017 May 17;6(9):e1323619. doi: 10.1080/2162402X.2017.1323619. eCollection 2017.
: DNA demethylating agents have shown clinical effectiveness in hematological and solid tumors. This trial tested the safety, efficacy, and treatment outcomes of decitabine-based chemotherapy or combined with immunotherapy in recurrent ovarian cancer patients. : Fifty-five patients with recurrent ovarian cancer were enrolled and 52 were assessable for clinical response and survival. Patients either received 5-d decitabine treatment, followed by reduced-dose of paclitaxel/carboplatin administration (DTC cohort), or the aforementioned regimen combined with cytokine-induced killer cells therapy (DTC+CIK cohort). The primary end point was clinical response rate and progression-free survival (PFS). Secondary evaluation included safety assessment and overall survival (OS). : Disease control rate (DCR) and objective response rate (ORR) were 73.91% and 23.91% in disease measurable patients by RECIST criteria, totally 76.92% and 30.77%, including disease non-measurable patients, which were higher in platinum-resistant/refractory patients. Clinical benefits could be associated with the number of DAC treatment cycles and the inclusion of CIK immunotherapy. In DTC+CIK cohort, DCR and ORR reached 100% and 58.30%, respectively. Notably, DTC+CIK treatment in platinum-resistant/refractory patients had an ORR of 87.50%. Consistently, PFS was longer in platinum-resistant/refractory patients comparing with that of platinum-sensitive patients. PFS and OS were 8 and 19 mo in platinum-resistant/refractory patients with DTC+CIK therapy. The most common toxicities were nausea, anorexia, fatigue, neutropenia, and anemia; many of which were grade 1-2. : Low-dose DAC/paclitaxel/carboplatin regimen demonstrates disease benefit, especially in patients with platinum-resistant/refractory ovarian cancer, and might show remarkable clinical response when combined with adoptive immunotherapy in platinum-resistant/refractory ovarian cancer patients.
DNA去甲基化剂已在血液系统肿瘤和实体瘤中显示出临床疗效。本试验测试了以地西他滨为基础的化疗或联合免疫疗法在复发性卵巢癌患者中的安全性、疗效和治疗结果。：招募了55例复发性卵巢癌患者，其中52例可评估临床反应和生存情况。患者要么接受5天地西他滨治疗，随后给予减量的紫杉醇/卡铂给药（DTC队列），要么接受上述方案联合细胞因子诱导的杀伤细胞疗法（DTC+CIK队列）。主要终点是临床反应率和无进展生存期（PFS）。次要评估包括安全性评估和总生存期（OS）。：根据RECIST标准，在可测量疾病的患者中，疾病控制率（DCR）和客观缓解率（ORR）分别为73.91%和23.91%，包括不可测量疾病的患者在内，总体分别为76.92%和30.77%，在铂耐药/难治性患者中更高。临床获益可能与DAC治疗周期数以及CIK免疫疗法的纳入有关。在DTC+CIK队列中，DCR和ORR分别达到100%和58.30%。值得注意的是，铂耐药/难治性患者接受DTC+CIK治疗的ORR为87.50%。同样，铂耐药/难治性患者的PFS比铂敏感患者更长。接受DTC+CIK治疗的铂耐药/难治性患者的PFS和OS分别为8个月和19个月。最常见的毒性反应是恶心、厌食、疲劳、中性粒细胞减少和贫血；其中许多为1-2级。：低剂量DAC/紫杉醇/卡铂方案显示出疾病获益，尤其是在铂耐药/难治性卵巢癌患者中，并且在铂耐药/难治性卵巢癌患者中与过继性免疫疗法联合使用时可能显示出显著的临床反应。
