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A randomized phase II trial of interleukin-2 in combination with four different doses of bryostatin-1 in patients with renal cell carcinoma

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Summary

Purpose: Bryostatin-1 is a PKC modulator with direct anti-tumor activity and immunomodulatory properties. We combined different doses of Bryostatin-1 with IL-2 to determine effects on clinical response rate and T cell phenotype in patients with advanced kidney cancer. Experimental Design: IL-2 naïve patients were given 11×106 IU subcutaneously of IL-2 on days 1–4, 8–11, and 15–18 of every 28-day cycle. Twenty four patients were randomized to treatment cohorts of 5, 15 or 25 mcg/m2 of Bryostatin-1 on days 1, 8 and 15, starting in the second cycle. An additional nine, non-randomized patients were given 35 mcg/m2. Lymphocytes were analyzed for number, activation status, and production of IL-2, IL-4 and IFN-γ. Response evaluation was performed every 3 cycles. Results: Common grade 3 toxicities included fatigue (5), nausea/vomiting (5), myopathy (3), dyspnea (3), and syncope (3). Four patients, in the two highest dose cohorts, demonstrated evidence of tumor shrinkage, although there was only 1 objective PR. The median time to progression was 104 days (95% CI 88–120) and the median survival was 452 days (95% CI = 424–480). There was no significant boosting effect of Bryostatin-1 on lymphocytes. Conclusions: The addition of Bryostatin-1 to IL-2 was well tolerated, but the overall response rate was low (3.2%), indicating that further studies with this combination are not warranted.

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago

    Amy C. Peterson, Helena Harlin, Everett Vokes, Thomas F. Gajewski & Walter M. Stadler

  2. Department of Health Studies, The University of Chicago, Chicago

    Theodore Karrison

  3. Nevada Cancer Institute, Las Vegas, Nevada

    Nicholas J. Vogelzang

  4. Oncology/Hematology Associates, Peoria, IL

    James A. Knost & John W. Kugler

  5. Oncology Care Associates, St. Joseph, MI, 49085

    Eric Lester

  6. University of Chicago Cancer Research Center, The University of Chicago, Chicago

    Everett Vokes & Walter M. Stadler

  7. Department of Pathology, The University of Chicago, Chicago

    Thomas F. Gajewski

  8. Department of Surgery, Section of Urology, The University of Chicago, Chicago

    Walter M. Stadler

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  1. Amy C. Peterson
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  2. Helena Harlin
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  3. Theodore Karrison
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  4. Nicholas J. Vogelzang
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  5. James A. Knost
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  6. John W. Kugler
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  7. Eric Lester
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  8. Everett Vokes
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  9. Thomas F. Gajewski
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  10. Walter M. Stadler
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for the University of Chicago Phase II Consortium

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Peterson, A.C., Harlin, H., Karrison, T. et al. A randomized phase II trial of interleukin-2 in combination with four different doses of bryostatin-1 in patients with renal cell carcinoma. Invest New Drugs 24, 141–149 (2006). https://doi.org/10.1007/s10637-006-5935-4

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  • DOI: https://doi.org/10.1007/s10637-006-5935-4

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