西南肿瘤学组S0826：SCH 727965（NSC 727135，DINACICLIB）的2期试验，IV期黑色素瘤患者
Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma
影响因子:5.10000
分区:医学1区 Top / 肿瘤学2区
发表日期:2025 Jan 01
作者:
Christopher D Lao, James Moon, Vincent T Ma, John P Fruehauf, Lawrence E Flaherty, Martin J Bury, William G Martin, Howard Gross, Wallace Akerley, Judith O Hopkins, Sapna P Patel, Vernon K Sondak, Antoni Ribas
摘要
细胞周期抑制是某些癌症的已建立治疗方法。依赖细胞周期蛋白依赖性激酶抑制剂SCH 727965（NSC 747135; dinaciclib）的多中心，单臂2阶段试验（ClinicalStrials.gov识别剂NCT00937937）在转移性蜂窝瘤中进行临床瘤的患者，将在临床瘤中进行过多的梅拉氏症，将其用于转移性的梅兰瘤，将进行转移性的患者，将其用于转移性的梅兰氏菌，并进行脑膜瘤的患者。对先前的治疗方法，Zubrod的性能状态为0-1和足够的器官功能。 SCH 727965 50 mg/m2每3周静脉注射，直到进展。共同主要终点是1年的总生存期（OS）和6个月的无进展生存期（PFS）。从2009年7月1日至2010年11月1日，在24个机构中招募了七十二名患者。 68％的患者患有M1C疾病，43％的患者乳酸脱氢酶水平升高。 28名患者（39％）经历了4级不良事件，包括20例中性粒细胞减少症。可以评估67例患者以进行反应。在67例患者中，零有反应（95％置信区间[CI]，0％-5％），在21％的患者中观察到稳定的疾病。估计的中位PFS为1.4个月（95％CI，1.4-1.5个月），而6个月的PFS率为6％（2％-13％）。中位OS为8.2个月（95％CI，5.5-10.5个月），1年OS率为38％（95％CI，26％-49％）。这项多中心，美国国家癌症研究所癌症研究所评估计划赞助的SCH 727965试验是在当前有效的治疗中进行的，该试验是对有效的治疗的，该试验是有效的糖尿病。尽管拒绝了1年OS的零假设，但PFS的最小影响和实质性毒性表明该方案缺乏作为单一药物的进一步研究的理由。
Abstract
Cell cycle inhibition is an established therapeutic approach for some cancers. A multicenter, single-arm, phase 2 trial (ClinicalTrials.gov identifier NCT00937937) of the cyclin-dependent kinase inhibitor SCH 727965 (NSC 747135; dinaciclib) was conducted in patients with metastatic melanoma to determine its clinical activity.Patients with metastatic melanoma of cutaneous or mucosal origin were eligible if they had zero to one previous treatments, a Zubrod performance status of 0-1, and adequate organ function. SCH 727965 50 mg/m2 was given intravenously every 3 weeks until progression. Co-primary end points were 1-year overall survival (OS) and 6-month progression-free survival (PFS).Seventy-two patients were enrolled from July 1, 2009, to November 1, 2010, at 24 institutions. Sixty-eight percent of patients had M1c disease, and 43% had elevated lactate dehydrogenase levels. Twenty-eight patients (39%) experienced grade 4 adverse events, including 20 cases of neutropenia. Sixty-seven patients were evaluable for response. There was a response in zero of 67 patients (95% confidence interval [CI], 0%-5%), and stable disease was observed in 21%. The estimated median PFS was 1.4 months (95% CI, 1.4-1.5 months), and the 6-month PFS rate was 6% (2%-13%). The median OS was 8.2 months (95% CI, 5.5-10.5 months), and the 1-year OS rate was 38% (95% CI, 26%-49%).This multicenter, US National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial of SCH 727965 was conducted at a time when the current generation of effective therapies for melanoma were not available. Although the null hypothesis of 1-year OS was rejected, the minimal PFS impact and substantive toxicity indicated that this regimen lacks justification for further investigation as a single agent.