Dexamethasone plus somatostatin-analog manipulation as bone metastasis microenvironment-targeting therapy for the treatment of castration-resistant prostate cancer: a meta-analysis of uncontrolled studies

Abstract

Background: Antisurvival factor therapy for prostate cancer cells (ASF) in castration-resistant prostate cancer, is a hormonal manipulation consisting of a somatostatin analog, which reduces the growth hormone-dependent, systemic IGF-1 production and of oral dexamethasone, which supresses the urokinase type plasminogen activator -mediated "local" increase of IGF-1 bioavailability in the bone metastases, while the patients continue on a luteinizing hormone-releasing hormone analog therapy.

Aim: To revisit relevant evidence and provide a quantitative summary estimate of ASF efficacy.

Materials and methods: A structured review of relevant literature and a meta-analysis of uncontrolled studies and cohorts within trials was carried out at tertiary academic centers. A computerized literature search was conducted in the electronic database Medline from inception to January 2012. To be eligible for inclusion, a study had to report data on the efficacy of ASF in the treatment of castration-resistant prostate cancer, independently of study design or duration. Data synthesis was performed using restricted maximum-likelihood random effects model.

Results: Four studies fulfilled the inclusion criteria and were used for the evidence synthesis. The probability of a partial response within six months (defined as at least a 50% decrease from baseline prostate-specific antigen concentrations) was 59.5% (95% confidence interval, 49.3% to 69.3%). No evidence of heterogeneity was noted (I(2) 0%). The response noted did not persist over time (median progression-free survival of seven months and median overall survival of 16 months). The uncontrolled nature of the evidence and the paucity of other outcomes of interest need to be taken into account in the interpretation of the results.

Conclusion: ASF manipulation is a safe alternative to standard therapy and induces partial remission lasting for at least six months. This partial response is consistently accompanied with an improvement in bone pain, performance status and quality of life.