Effect of the somatostatin analog octreotide acetate on circulating insulin-like growth factor-1 and related peptides in patients with non-metastatic castration-resistant prostate cancer: results of a phase II study.

Journal Article (Journal Article)

Background

Insulin-like growth factor (IGF) mediated signaling has been implicated in the growth of many tumor types including prostate cancer, and it is hypothesized that lowering circulating IGF levels in men with castration resistant prostate cancer (CRPC) will slow tumor growth. In this study, the efficacy of depot octreotide acetate was prospectively evaluated in patients with CRPC.

Methods

Eligible patients had progressive non-metastatic CRPC. Octreotide acetate 30 mg was administered intramuscularly every 28 days. Changes in PSA, IGF-1, IGF-2, IGF binding protein-1 (IGFBP-1), and IGFBP-3 were evaluated over time.

Results

Accrual was stopped early after a pre-planned interim analysis showed no prostate specific antigen (PSA) declines after 3 cycles of treatment among the first 13 patients enrolled. Median baseline PSA and IGF-1 measurements were 36.2 ng/ml and 162.6 ng/ml, respectively, and median time on treatment was 13 weeks. Radiographic progression occurred in 7 patients, PSA-only progression occurred in 5 patients, and 1 patient was taken off the study due to a grade 3 drug interaction. After 3 cycles of treatment IGF-1 significantly declined with a median -34.5% (P = 0.01) and IGFBP-1 significantly increased with a median 76.3% (P = 0.046). IGF-2 and IGFBP-3 were not significantly changed from baseline.

Conclusions

Octreotide acetate significantly lowers IGF-1 and raises IGFBP-1 levels in patients with non-metastatic CRPC, but does not result in sustained declines in PSA. While treatment with single-agent octreotide may not be warranted, its inclusion in combination regimens directly targeting the IGF-1 receptor on tumor cells may be of interest.

Full Text

Duke Authors

Cited Authors

  • Friedlander, TW; Weinberg, VK; Small, EJ; Sharib, J; Harzstark, AL; Lin, AM; Fong, L; Ryan, CJ

Published Date

  • July 2012

Published In

Volume / Issue

  • 30 / 4

Start / End Page

  • 408 - 414

PubMed ID

  • 20884247

Electronic International Standard Serial Number (EISSN)

  • 1873-2496

International Standard Serial Number (ISSN)

  • 1078-1439

Digital Object Identifier (DOI)

  • 10.1016/j.urolonc.2010.06.014

Language

  • eng