It is important to determine whether an increase in Chromogranin A levels and neuroendocrine (NE) cell activation are associated with progression towards on hormone-independent prostate-cancer. We proposed a combination of estrogens and somatostatin analogues as therapy of NE activation in hormone-independent prostate cancer. The combined therapy with ethinyl estradiol and lanreotide offered objective and symptomatic responses in patients with limited treatment options and refractoriness to conventional hormonal therapy strategies; in particular, it offered a median overall survival that was superior to the 10–month median survival in patients with hormone refractory disease. This combined therapy also sustains the new concept in cancer treatment in which therapies may target not only cancer cells but also its microenvironment, which can yield protection against apoptosis.
CarrollP.R., AltweinJ., BrawleyO.Management of disseminated prostate cancer. In: DenisL., BartschG., KhouryS., MuraiM., PartinA., eds. 3rd International Consultation on Prostate Cancer - Paris.United Kingdom: Plymbridge Distributors Ltd, 2003: 251–84.
2.
RobertsonC.N., RobersonK.M., PadillaG.M., O'BrienE.T., CookJ.M., FineR.L.Induction of apoptosis by diethylstilbestrol in hormone- insensitive prostate cancer cells.J Natl Cancer Inst1996; 88: 908–17.
3.
RobinsonM.R., SmithP.H., RichardsB., NewlingD.W., de PauwM., SylvesterR.The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic.Eur Urol1995; 28: 273–83.
4.
HedlundP.O., HenrikssonP.Parenteral estrogen versus total androgen ablation in the treatment of advanced prostate carci- noma: effects on overall survival and cardiovascular mortality. The Scandinavian Prostatic Cancer Group (SPCG)-5 Trial Study.Urology2000; 55: 328–33.
5.
OckrimJ.L., LalaniE-N, LaniadoM.E., CarterS.S., AbelP.D.Transdermal estrogen therapy for advanced prostate cancer-for- ward to the past?J Urol2002; 167: 175 (Abstract 702).
ReubiJ.C., WasarB., SchaerJ.C., LaissueJ.A.Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands.Eur J Nucl Med2001; 28: 836–46.
8.
HejnaM., SchmidingerM., RadererM.The clinical role of somatostatin analogues as antineoplastic agents: much ado about nothing?Ann Oncol2002; 13: 653–68.
9.
KoutsilierisM., MitsiadesC., DimopoulusT.Combination of dexamethasone and a somatostatine analogue in the treatment of advanced prostate cancer.Expert Opin investig Drugs2002; 11: 283–93.
10.
KoutsilierisM., MitsiadesC., DimopoulusT., IannidisA., NtounisA., LambouT.A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LH-RH analog in androgen ablation-refractory prostate cancer patients.J Clin Endocrinol Metab2001; 86: 5729–36.
11.
JongsmaJ., OomenM.H., NoordzijM.A.Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines.Prostate2000; 42: 34–44.
12.
SegalG., CohenF., HuffejeeZ., SavageN.Bcl2 protooncogene expression in prostate cancer and its relationship to the pro- static neuroendocrine cell.Arch Pathol Lab Med1994; 118: 616–8.
13.
LambertsS.W., van der LelyA.J., HoflandL.J.New somatostatin analogs: will they fulfill old promises?Eur J Endocrinol2002; 146: 701–5.
14.
DizeyiN., KonradL., BjartellA.Localozation and mRNA Expession of somatostatin receptor subtypes in human prostatic tissue and prostate cancer cell lines.Urol Oncol2002; 7: 91–8.
15.
LescheS., LehmannD.Differential Effect of Octreotide and Pasireotide on Somatostatin Receptor Internalization and Trafficking in Vitro.J Clin Endocrinol Metab.2009, 94(2): 654–661.
16.
Di SilverioF., SciarraA.Combination therapy of ethinylestradiol and somatostatin analogue reintroduces objective clinical responses and decrease chromogranin A in patients with androgen ablation refractory prostate cancer.J Urol2003; 170: 1812–6.
17.
SciarraA., MariottiG., GentileV.Neuroendocrine differentiation in human prostate tissue: is it detectable and treatable?BJU Int2003; 91: 438–45.
