西南肿瘤学组 S0826:SCH 727965(NSC 727135,dinaciclib)治疗 IV 期黑色素瘤患者的 2 期试验。

IF 6.1 2区 医学 Q1 ONCOLOGY
Cancer Pub Date : 2024-09-29 DOI:10.1002/cncr.35587
Christopher D. Lao MD, James Moon MS, Vincent T. Ma MD, John P. Fruehauf MD, Lawrence E. Flaherty MD, Martin J. Bury MD, William G. Martin MD, Howard Gross MD, Wallace Akerley MD, Judith O. Hopkins MD, Sapna P. Patel MD, Vernon K. Sondak MD, Antoni Ribas MD, PhD
{"title":"西南肿瘤学组 S0826:SCH 727965(NSC 727135,dinaciclib)治疗 IV 期黑色素瘤患者的 2 期试验。","authors":"Christopher D. Lao MD,&nbsp;James Moon MS,&nbsp;Vincent T. Ma MD,&nbsp;John P. Fruehauf MD,&nbsp;Lawrence E. Flaherty MD,&nbsp;Martin J. Bury MD,&nbsp;William G. Martin MD,&nbsp;Howard Gross MD,&nbsp;Wallace Akerley MD,&nbsp;Judith O. Hopkins MD,&nbsp;Sapna P. Patel MD,&nbsp;Vernon K. Sondak MD,&nbsp;Antoni Ribas MD, PhD","doi":"10.1002/cncr.35587","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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<sup>2</sup> 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).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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%).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 1","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694162/pdf/","citationCount":"0","resultStr":"{\"title\":\"Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma\",\"authors\":\"Christopher D. Lao MD,&nbsp;James Moon MS,&nbsp;Vincent T. Ma MD,&nbsp;John P. Fruehauf MD,&nbsp;Lawrence E. Flaherty MD,&nbsp;Martin J. Bury MD,&nbsp;William G. Martin MD,&nbsp;Howard Gross MD,&nbsp;Wallace Akerley MD,&nbsp;Judith O. Hopkins MD,&nbsp;Sapna P. Patel MD,&nbsp;Vernon K. Sondak MD,&nbsp;Antoni Ribas MD, PhD\",\"doi\":\"10.1002/cncr.35587\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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<sup>2</sup> 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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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%).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":138,\"journal\":{\"name\":\"Cancer\",\"volume\":\"131 1\",\"pages\":\"\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694162/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cncr.35587\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cncr.35587","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:细胞周期抑制是一种治疗某些癌症的成熟方法。为了确定细胞周期依赖性激酶抑制剂SCH 727965(NSC 747135;dinaciclib)的临床活性,我们在转移性黑色素瘤患者中开展了一项多中心、单臂、2期试验(ClinicalTrials.gov标识符NCT00937937):皮肤或粘膜转移性黑色素瘤患者,如果既往治疗次数为零到一次,祖布罗德表现状态为0-1,且器官功能正常,则符合条件。SCH 727965 50 mg/m2每3周静脉注射一次,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):从 2009 年 7 月 1 日到 2010 年 11 月 1 日,24 家机构共招募了 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%)出现了4级不良反应,其中包括20例中性粒细胞减少症。67名患者可进行反应评估。67例患者中0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% 置信区间 [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SCH 727965多中心试验是在新一代黑色素瘤有效疗法尚未问世时进行的。虽然1年OS的零假设被否定,但PFS的影响极小,毒性也很大,这表明该方案作为单药缺乏进一步研究的理由。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

Background

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.

Methods

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).

Results

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%).

Conclusions

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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cancer
Cancer 医学-肿瘤学
CiteScore
13.10
自引率
3.20%
发文量
480
审稿时长
2-3 weeks
期刊介绍: The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信