Open Access

A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer

  • Authors: Terence W. Friedlander, Vivian K. Weinberg, Yong Huang, Joanna T. Mi, Carl G. Formaker, Eric J. Small, Andrea L. Harzstark, Amy M. Lin, Lawrence Fong, Charles J. Ryan
  • View Affiliations

  • Published online on: Tuesday, October 4, 2011
  • Pages: 3-9
  • DOI: 10.3892/or.2011.1487

Abstract

Insulin-like growth factor (IGF)-mediated signaling is a newly recognized clinical target in prostate cancer, and it is hypothesized that blockade of the IGF receptor (IGF1R) will impair downstream signaling and slow tumor growth. In this study the efficacy of nordihydroguaiaretic acid (NDGA), a small molecule inhibitor of the IGF-1R, was prospectively evaluated in patients with non-metastatic hormone-sensitive prostate cancer (HSPC). Eligible patients had non-metastatic HSPC with a rising prostate-specific antigen (PSA) and a normal testosterone level. NDGA 2000 mg was given orally daily in 28 day cycles and treatment continued until PSA progression or toxicity. Accrual was stopped early after a pre-planned interim analysis showed no significant PSA declines after 3 cycles of treatment among the first 12 patients enrolled. Median time on treatment was 9 cycles (range 2-19) for 11 patients now off study; 1 patient continues to receive therapy and has been on study for 29 months. Seven patients experienced non-sustained declines in PSA ranging from 1.9 to 15.8% of baseline. PSADT lengthened by a median of 1.4 months for all evaluable patients when compared to pretreatment PSADT (range -6.1 to +19.8 months). Grade 3 events were rare and included nausea/vomiting, syncope due to dehydration, and elevated liver function tests in 1 patient, and cognitive disturbance in another patient. NDGA therapy lengthens median PSADT but does not induce significant PSA declines. Further study may require a placebo-control to determine if changes in PSADT are drug related.
Journal Cover

January 2012
Volume 27 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

2012 Impact Factor: 2.191
Ranked #33/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Friedlander, T., Weinberg, V., Huang, Y., Mi, J., Formaker, C., Small, E., Harzstark, A., Lin, A., Fong, L., & Ryan, C. (2012). A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer. Oncology Reports, 27(1), 3-9.
MLA
Friedlander, Weinberg, Huang, Mi, Formaker, Small, Harzstark, Lin, Fong, and Charles Ryan. "A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer." Oncology Reports Oncology Reports 27.1 (2012): 3-9.
Chicago
Friedlander, Weinberg, Huang, Mi, Formaker, Small, Harzstark, Lin, Fong, and Charles Ryan. "A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer." Oncology Reports Oncology Reports 27 no. 1 (2012): 3-9.