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

  • Amy C. Peterson
  • Helena Harlin
  • Theodore Karrison
  • Nicholas J. Vogelzang
  • James A. Knost
  • John W. Kugler
  • Eric Lester
  • Everett Vokes
  • Thomas F. Gajewski
  • Walter M. Stadler
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

Authors and Affiliations

  • Amy C. Peterson
    • 1
  • Helena Harlin
    • 1
  • Theodore Karrison
    • 2
  • Nicholas J. Vogelzang
    • 3
  • James A. Knost
    • 4
  • John W. Kugler
    • 4
  • Eric Lester
    • 5
  • Everett Vokes
    • 1
    • 6
  • Thomas F. Gajewski
    • 1
    • 7
  • Walter M. Stadler
    • 1
    • 6
    • 8
  1. 1.Department of Medicine, Section of Hematology/OncologyThe University of ChicagoChicago
  2. 2.Department of Health StudiesThe University of ChicagoChicago
  3. 3.Nevada Cancer InstituteLas Vegas
  4. 4.Oncology/Hematology AssociatesPeoria
  5. 5.Oncology Care AssociatesSt. Joseph
  6. 6.University of Chicago Cancer Research CenterThe University of ChicagoChicago
  7. 7.Department of PathologyThe University of ChicagoChicago
  8. 8.Department of Surgery, Section of UrologyThe University of ChicagoChicago