Dasatinib in previously treated metastatic colorectal cancer: a phase II trial of the University of Chicago Phase II Consortium

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• 作者：Manish R. Sharma (1)
  Kristen Wroblewski (2)
  Blase N. Polite (1)
  James A. Knost (3)
  James A. Wallace (1)
  Sanjiv Modi (4)
  Bethany G. Sleckman (5)
  David Taber (6)
  Everett E. Vokes (1)
  Walter M. Stadler (1)
  Hedy L. Kindler (1) hkindler@medicine.bsd.uchicago.edu
• 关键词：Colorectal cancer – ; Phase II trial – ; Dasatinib
• 刊名：Investigational New Drugs
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：30
• 期：3
• 页码：1211-1215
• 全文大小：161.7 KB
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• 作者单位：1. Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USA2. Department of Health Studies, University of Chicago, Chicago, IL, USA3. Illinois Cancer Care, Peoria, IL, USA4. Joliet Hematology/Oncology, Joliet, IL, USA5. St Johns Mercy Medical Center, St Louis, MO, USA6. Michiana Hematology/Oncology, South Bend, IN, USA
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Pharmacology and Toxicology
  
• 出版者：Springer Netherlands
• ISSN：1573-0646

文摘

Background Treatment options for metastatic colorectal cancer (CRC) are limited after a fluoropyrimidine, oxaliplatin and irinotecan; novel agents need to be explored in this setting. Dasatinib, an oral inhibitor of Src family kinases, inhibits proliferation in CRC cell lines and has antitumor activity in CRC xenograft models. Patients and methods We conducted a multi-center phase II trial of dasatinib in unresectable, previously-treated metastatic CRC patients. No more than 2 prior chemotherapy regimens were permitted, which must have contained a fluoropyrimidine, oxaliplatin and irinotecan. The primary endpoint was progression-free survival (PFS) at 4 months. The Simon two-stage design required that at least 5 of the first 19 patients be progression-free at 4 months to expand to a second stage. Results Nineteen patients enrolled at 9 centers. The study was terminated after the first stage due to lack of efficacy. There were no objective responses; 1 patient (5%) had stable disease for 7.3 months. The PFS rate at 4 months was 5.3% (90% CI: 0.3, 22.6). Median PFS was 1.6 months (90% CI: 1.4, 1.8). Median overall survival was 5.1 months (90% CI: 2.4, 6.3). Grade 3/4 toxicities included fatigue in 16% of patients, and anemia, anorexia, nausea/vomiting and dyspnea in 11%. Conclusion Dasatinib is inactive as a single agent in previously treated metastatic CRC patients.