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, 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","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, 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\",\"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}
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.
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