Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (vapreotide) at the time of relapse.
ABSTRACT The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (vapreotide) at the time of relapse in patients with androgen independent prostate cancer.
Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48-102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17-91 months). A new remission period with a median duration of 10 months (range 2-29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group.
Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5 +/- 308.5 to 68.2 +/- 60.5 ng/ml (mean decline 71 +/- 8%; P < 0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62 +/- 0.48 to 0.37 +/- 0.69 and an increase in the Karnofsky performance status from 72.3 +/- 4.21 to 83.6 +/- 23.2 (P < 0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea.
Our results indicate that therapy with the somatostatin analog vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy.
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ABSTRACT: The insulin-like growth factor (IGF) signaling pathway has been implicated in prostate cancer (PCa) initiation, but its role in progression remains unknown. Among 5887 PCa patients (704 PCa deaths) of European ancestry from seven cohorts in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium, we conducted Cox kernel machine pathway analysis to evaluate whether 530 tagging single nucleotide polymorphisms (SNPs) in 26 IGF pathway-related genes were collectively associated with PCa mortality. We also conducted SNP-specific analysis using stratified Cox models adjusting for multiple testing. In 2424 patients (313 PCa deaths), we evaluated the association of prediagnostic circulating IGF1 and IGFBP3 levels and PCa mortality. All statistical tests were two-sided. The IGF signaling pathway was associated with PCa mortality (P = .03), and IGF2-AS and SSTR2 were the main contributors (both P = .04). In SNP-specific analysis, 36 SNPs were associated with PCa mortality with P trend less than .05, but only three SNPs in the IGF2-AS remained statistically significant after gene-based corrections. Two were in linkage disequilibrium (r (2) = 1 for rs1004446 and rs3741211), whereas the third, rs4366464, was independent (r (2) = 0.03). The hazard ratios (HRs) per each additional risk allele were 1.19 (95% confidence interval [CI] = 1.06 to 1.34; P trend = .003) for rs3741211 and 1.44 (95% CI = 1.20 to 1.73; P trend < .001) for rs4366464. rs4366464 remained statistically significant after correction for all SNPs (P trend.corr = .04). Prediagnostic IGF1 (HRhighest vs lowest quartile = 0.71; 95% CI = 0.48 to 1.04) and IGFBP3 (HR = 0.93; 95% CI = 0.65 to 1.34) levels were not associated with PCa mortality. The IGF signaling pathway, primarily IGF2-AS and SSTR2 genes, may be important in PCa survival.CancerSpectrum Knowledge Environment 05/2014; DOI:10.1093/jnci/dju085 · 14.07 Impact Factor
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ABSTRACT: The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of both IGF-I and IGF-II. The IGF-IR is expressed in most transformed cells, where it displays potent antiapoptotic, cell-survival, and transforming activities. IGF-IR expression is a fundamental prerequisite for the acquisition of a malignant phenotype, as suggested by the finding that IGF-IR-null cells (derived from IGF-IR knock-out embryos) are unable to undergo transformation when exposed to cellular or viral oncogenes. This review article will focus on the underlying molecular mechanisms that are responsible for the normal, physiological control of IGF-IR gene expression, as well as the cellular pathways that underlie its aberrant expression in cancer. Examples from the clinics will be presented, including a description of how the IGF system is involved in breast, prostate, pediatric, and gynecological cancers. Finally, current attempts to target the IGF-IR as a therapeutic approach will be described.
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ABSTRACT: Somatostatin is a hormone that regulates several physiological cell processes via specific receptors expressed throughout the body, in particular by nerve cells, many neuroendocrine cells, and cells mediating inflammation and immune responses. Somatostatin receptor scintigraphy achieved by administration of somatostatin labeled with a γ-emitting isotope has become an integral part of the work-up and treatment monitoring program in patients with neuroendocrine tumors, most of which overexpress somatostatin receptors. Several studies have convincingly established that somatostatin receptor scintigraphy benefits patients with a number of chronic inflammatory diseases, including sarcoidosis and other granulomatous diseases. In the evaluation of hematological diseases and detection of mesenchymatous tumors manifesting as oncogenic osteomalacia, the preliminary results are sufficiently promising to warrant larger studies aimed at defining the role for this noninvasive whole-body imaging technique. In the treatment area, the development of somatostatin analogs with antisecretory and antiproliferative effects has radically changed the management of gastroenteropancreatic neuroendocrine tumors and pituitary tumors. The antiinflammatory and analgesic effects of these drugs remain incompletely understood but may prove useful in a number of autoimmune diseases.Revue du Rhumatisme 12/2004; 71(12):1136-1142. DOI:10.1016/j.rhum.2004.02.006