细胞周期抑制是某些癌症的既定治疗方法。细胞周期蛋白依赖性激酶抑制剂 SCH 727965（NSC 747135；dinaciclib）在转移性黑色素瘤患者中进行了一项多中心、单臂、2 期试验（ClinicalTrials.gov 标识符 NCT00937937），以确定其临床活性。如果皮肤或粘膜来源的患者之前接受过 0 到 1 次治疗，Zubrod 表现状态为 0-1，并且有足够的器官功能，则符合资格。每 3 周静脉注射 SCH 727965 50 mg/m2，直至出现进展。共同主要终点是 1 年总生存期 (OS) 和 6 个月无进展生存期 (PFS)。从 2009 年 7 月 1 日到 2010 年 11 月 1 日，在 24 个机构招募了 72 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，其中包括 20 例中性粒细胞减少症。可评估 67 名患者的反应。 67 名患者中有 0 名出现缓解（95% 置信区间 [CI]，0%-5%），21% 的患者病情稳定。估计中位 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%）。这项多中心、美国国家癌症研究所癌症治疗评估计划SCH 727965 赞助的试验是在当前一代有效的黑色素瘤治疗方法尚不可用时进行的。尽管 1 年 OS 的零假设被拒绝，但最小的 PFS 影响和实质性毒性表明该方案缺乏作为单一药物进行进一步研究的理由。© 2024 作者。 《癌症》由 Wiley periodicals LLC 代表美国癌症协会出版。

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.© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.