Investigational New Drugs

, Volume 24, Issue 2, pp 141–149

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

Authors

  • Amy C. Peterson
    • Department of Medicine, Section of Hematology/OncologyThe University of Chicago
  • Helena Harlin
    • Department of Medicine, Section of Hematology/OncologyThe University of Chicago
  • Theodore Karrison
    • Department of Health StudiesThe University of Chicago
  • Nicholas J. Vogelzang
    • Nevada Cancer Institute
  • James A. Knost
    • Oncology/Hematology Associates
  • John W. Kugler
    • Oncology/Hematology Associates
  • Eric Lester
    • Oncology Care Associates
  • Everett Vokes
    • Department of Medicine, Section of Hematology/OncologyThe University of Chicago
    • University of Chicago Cancer Research CenterThe University of Chicago
  • Thomas F. Gajewski
    • Department of Medicine, Section of Hematology/OncologyThe University of Chicago
    • Department of PathologyThe University of Chicago
  • Walter M. Stadler
    • Department of Medicine, Section of Hematology/OncologyThe University of Chicago
    • University of Chicago Cancer Research CenterThe University of Chicago
    • Department of Surgery, Section of UrologyThe University of Chicago
Article

DOI: 10.1007/s10637-006-5935-4

Cite this article as:
Peterson, A.C., Harlin, H., Karrison, T. et al. Invest New Drugs (2006) 24: 141. doi:10.1007/s10637-006-5935-4

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. ExperimentalDesign: 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.

Key words

BryostatinInterleukin-2Renal cell cancerPhase II trial

Copyright information

© Springer Science + Business Media, Inc. 2006