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A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium

  • PHASE II STUDIES
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Summary

Background Sorafenib is an oral multikinase inhibitor that blocks cell proliferation via the ERK pathway and angiogenesis via the VEGF pathway. This phase II trial was conducted to determine the efficacy and tolerability of sorafenib for the treatment of patients with metastatic urothelial cancer (UC) who had not had prior chemotherapy for advanced disease. Patients and Methods Seventeen chemo-naïve UC patients with adequate performance status and organ function were treated with sorafenib 400 mg twice daily on a continuous basis until progression or unacceptable toxicity. The primary endpoint was objective tumor response rate as measured by RECIST criteria. Secondary endpoints included rate of prolonged stable disease (>3 months), time to progression, median and 1 yr survival and safety and tolerability. Results There were no objective responses. Only one patient had stable disease by RECIST criteria and remained on treatment more than 3 months. Three patients had stable disease by RECIST criteria but were on treatment less than 3 months due to progressive disease (PD) or adverse events (AE). Eight patients had PD by RECIST criteria as their best overall response. Two patients had symptomatic PD prior to cycle 2 evaluation, and three patients were inevaluable (1 death, 1 AE, 1 withdrew consent).The time to progression was 1.9 months (range 0.7–8.7 months) and median survival was 5.9 months. The most common grade 3+ toxicities were abdominal pain, back pain, hand-foot reaction and bladder infection. Conclusions Sorafenib does not show sufficient activity as a single agent in first-line metastatic urothelial cancer to warrant further investigation.

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Authors and Affiliations

  1. Princess Margaret Hospital, Phase II Consortium, 610 University Avenue, Suite 5-222, Toronto, Ontario, M5G 2M9, Canada

    Srikala S. Sridhar, Ian F. Tannock, Lisa Wang, Chantale Blattler & Malcolm J. Moore

  2. London Regional Cancer Center, London, ON, Canada

    Eric Winquist

  3. Odette Cancer Center, Toronto, ON, Canada

    Andrea Eisen

  4. Juravinski Cancer Center, Hamilton, ON, Canada

    Sebastien J. Hotte, Elaine McWhirter & Som D. Mukherjee

  5. Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA

    John J. Wright

Authors
  1. Srikala S. Sridhar
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  2. Eric Winquist
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  3. Andrea Eisen
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  4. Sebastien J. Hotte
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  5. Elaine McWhirter
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  6. Ian F. Tannock
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  7. Som D. Mukherjee
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  8. Lisa Wang
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  9. Chantale Blattler
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  10. John J. Wright
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  11. Malcolm J. Moore
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Correspondence to Srikala S. Sridhar.

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Presentations: American Society of Clinical Oncology (ASCO) - 2008 Genitourinary Cancers Symposium

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Sridhar, S.S., Winquist, E., Eisen, A. et al. A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium. Invest New Drugs 29, 1045–1049 (2011). https://doi.org/10.1007/s10637-010-9408-4

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  • DOI: https://doi.org/10.1007/s10637-010-9408-4

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