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

  • PHASE II STUDIES
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Summary

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.

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Funding source

NCI Grant N01-CM-62201.

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Authors and Affiliations

  1. Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637-1470, USA

    Manish R. Sharma, Blase N. Polite, James A. Wallace, Everett E. Vokes, Walter M. Stadler & Hedy L. Kindler

  2. Department of Health Studies, University of Chicago, Chicago, IL, USA

    Kristen Wroblewski

  3. Illinois Cancer Care, Peoria, IL, USA

    James A. Knost

  4. Joliet Hematology/Oncology, Joliet, IL, USA

    Sanjiv Modi

  5. St Johns Mercy Medical Center, St Louis, MO, USA

    Bethany G. Sleckman

  6. Michiana Hematology/Oncology, South Bend, IN, USA

    David Taber

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  1. Manish R. Sharma
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  2. Kristen Wroblewski
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  3. Blase N. Polite
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  4. James A. Knost
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  7. Bethany G. Sleckman
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  8. David Taber
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  9. Everett E. Vokes
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  10. Walter M. Stadler
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  11. Hedy L. Kindler
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Correspondence to Hedy L. Kindler.

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Sharma, M.R., Wroblewski, K., Polite, B.N. et al. Dasatinib in previously treated metastatic colorectal cancer: a phase II trial of the University of Chicago Phase II Consortium. Invest New Drugs 30, 1211–1215 (2012). https://doi.org/10.1007/s10637-011-9681-x

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  • DOI: https://doi.org/10.1007/s10637-011-9681-x

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