Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade

Andrew S. Kraft, Elizabeth Garrett-Mayer, Amy E. Wahlquist, Ali Golshayan, Chien Shing Chen, William Butler, James Bearden, Michael Lilly

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

A single arm phase II trial of single-agent bortezomib (BZM) alone or combined with hormone blockade was conducted in patients with early PSA recurrence after definitive local therapy. The primary endpoint of this study was to determine the time to PSA relapse after BZM therapy alone or when BZM was combined with hormone blockade. The secondary endpoint was to determine the safety of combination therapy. Part A of the treatment schedule consisted of three cycles of BZM 1.3 mg/m2 IV given on days 1, 4, 8 and 11. If patients progressed on Part A, they were entered on Part B which consisted of a single dose of LH-RH antagonist, daily oral antiandrogen, and weekly BZM 1.3 mg/m 2 for 3 out of 4 weeks for a total of 3 months. BZM treatment significantly decreased the slope of the log PSA (p = 0.024) demonstrating that this agent alone was capable of slowing the rise of the PSA. Of eight patients treated with BZM alone five had stable disease, two progressed and one went off study secondary to toxicity. The major toxicity was neurotoxicity requiring discontinuation of therapy in three patients and treatment interruption in nine patients. Of those receiving Parts A and B or B only, there were 11 of 15 CRs with the average time to progression of 5.5 months. BZM treatment can change the slope of PSA rise and can be combined with hormone deprivation therapy without significant additional side effects; these agents are associated with a median time to CR of 42 days.

Original languageEnglish (US)
Pages (from-to)119-124
Number of pages6
JournalCancer Biology and Therapy
Volume12
Issue number2
DOIs
StatePublished - Jul 15 2011
Externally publishedYes

Keywords

  • Bortezomib
  • Combination therapy
  • Hormone blockade
  • Neurotoxicity
  • Prostate specific antigen
  • Recurrent prostate cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Kraft, A. S., Garrett-Mayer, E., Wahlquist, A. E., Golshayan, A., Chen, C. S., Butler, W., Bearden, J., & Lilly, M. (2011). Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade. Cancer Biology and Therapy, 12(2), 119-124. https://doi.org/10.4161/cbt.12.2.15723