西南肿瘤组S0826：一项关于SCH 727965（NSC 727135，dinaciclib）在IV期黑色素瘤患者中的二期临床试验

Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma

CANCER

影响因子:5.1

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

DOI: 10.1002/cncr.35587

摘要

细胞周期抑制是某些癌症的成熟治疗策略。一项多中心单臂二期试验（ClinicalTrials.gov 编号NCT00937937）评估了环素依赖激酶抑制剂SCH 727965（NSC 747135；dinaciclib）在转移性黑色素瘤患者中的临床活性。符合条件的患者为源自皮肤或黏膜的转移性黑色素瘤，既往治疗次数为零到一次，Zubrod表现状态为0-1，且器官功能充分。每3周静脉给予50 mg/m2 SCH 727965，直至疾病进展。主要终点包括1年总生存率（OS）和6个月无进展生存率（PFS）。从2009年7月1日至2010年11月1日，24个机构共入组72例患者。68%的患者为M1c期，43%的患者血清乳酸脱氢酶升高。28例（39%）患者出现4级不良反应，包括20例中性粒细胞减少。67例患者可评估反应。在67例中未观察到任何部分缓解（95% CI，0%-5%），稳定疾病者21%。估算中位PFS为1.4个月（95% CI，1.4-1.5个月），6个月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%）。这项由美国国家癌症研究所癌症治疗评估项目支持的多中心试验在当前有效黑色素瘤治疗手段尚未普及的背景下进行。虽然拒绝了1年总生存率的原假设，但PFS的最小影响及显著毒性表明该方案作为单药治疗缺乏进一步研究的依据。

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.