Lao Christopher D, Moon James, Ma Vincent T, Fruehauf John P, Flaherty Lawrence E, Bury Martin J, Martin William G, Gross Howard, Akerley Wallace, Hopkins Judith O, Patel Sapna P, Sondak Vernon K, Ribas Antoni
Rogel Cancer Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Bristol Myers Squibb, Princeton, New Jersey, USA.
Cancer. 2025 Jan 1;131(1):e35587. doi: 10.1002/cncr.35587. Epub 2024 Sep 29.
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/m 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.
细胞周期抑制是某些癌症已确立的治疗方法。一项关于细胞周期蛋白依赖性激酶抑制剂SCH 727965（NSC 747135；地西他滨）的多中心、单臂、2期试验（ClinicalTrials.gov标识符NCT00937937）在转移性黑色素瘤患者中开展，以确定其临床活性。
皮肤或黏膜来源的转移性黑色素瘤患者若既往接受过零至一次治疗、Zubrod体能状态为0 - 1且器官功能良好，则符合入组条件。每3周静脉注射一次50 mg/m²的SCH 727965，直至病情进展。共同主要终点为1年总生存期（OS）和6个月无进展生存期（PFS）。
2009年7月1日至2010年11月1日期间，24家机构共纳入72例患者。68%的患者患有M1c期疾病，43%的患者乳酸脱氢酶水平升高。28例患者（39%）发生4级不良事件，包括20例中性粒细胞减少症。67例患者可评估疗效。67例患者中无一例有反应（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%）。
这项由美国国立癌症研究所癌症治疗评估项目赞助的关于SCH 727965的多中心试验，是在尚无当前一代有效黑色素瘤治疗方法的情况下进行的。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，该方案作为单一药物缺乏进一步研究的依据。
