Restricted accessResearch articleFirst published online 2014-05
Somatostatin Analogs and Disease Control in Castration-resistant Prostate Cancer: Different Biological Behavior? Case Series and Review of the Literature
Castration-resistant prostate cancer is a recent biological behavior where disease can elude androgen deprivation therapy (ADT). Several pathways have been described, including neuroendocrine dedifferentiation. Patients with neuroendocrine dedifferentiation show an increase in chromogranin A (CgA) along with a PSA increase. Our aim was to evaluate the response of patients with castration-resistant prostate cancer and high CgA serum levels after treatment with inhibitors of neuroendocrine cells (somatostatin analogs) in combination with ADT.
Methods
From January 2009 to April 2011, 10 patients with castration-resistant prostate cancer and rising PSA levels along with a CgA increase were evaluated. The therapy was based on somatostatin analogs and LHRH anologs. Total PSA and CgA were measured every 2 months.
Results
In 9 of the 10 patients, a reduction of the values of pre-treatment CgA was detected, while a reduction of PSA was found in 8 patients. No grade 2 or higher toxicity was recorded. Only 3 patients had grade 1 gastrointestinal toxicity. Time to progression was 13 months.
Conclusion
Therapy with somatostatin analogs could increase the therapeutic window of ADT with a low toxicity profile in a subpopulation of patients with castration-resistant prostate cancer who experience a rise in CgA due to neuroendocrine regulation.
PetrylakD.P., TangenC.M., HussainM.H., LaraPNJr, JonesJ.A., TaplinM.E., BurchP.A., BerryD., MoinpourC., KohliM., BensonM.C., SmallE.J., RaghavanD., CrawfordE.D.: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med, 351: 1513–1520, 2004.
2.
TannockI.F., de WitR., BerryW.R., HortiJ., PluzanskaA., ChiK.N., OudardS., ThéodoreC., JamesN.D., TuressonI., RosenthalM.A., EisenbergerM.A.; TAX 327 Investigators: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med, 351: 1502–1512, 2004.
3.
KellyW.K., HalabiS., CarducciM., GeorgeD., MahoneyJ.F., StadlerW.M., MorrisM., KantoffP., MonkJ.P., KaplanE., VogelzangN.J., SmallE.J.: Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol, 30: 1534–1540, 2012.
4.
StanbroughM., BubleyG.J., RossK., GolubT.R., RubinM.A., PenningT.M., FebboP.G., BalkS.P.: Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res, 66: 2815–2825, 2006.
5.
MontgomeryR.B., MostaghelE.A., VessellaR., HessD.L., KalhornT.F., HiganoC.S., TrueL.D., NelsonP.S.: Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res, 68: 4447–4454, 2008.
6.
GuoZ., YangX., SunF., JiangR., LinnD.E., ChenH., ChenH., KongX., MelamedJ., TepperC.G., KungH.J., BrodieA.M., EdwardsJ., QiuY.: A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res, 69: 2305–2313, 2009.
7.
SunY., NiuJ., HuangJ.: Neuroendocrine differentiation in prostate cancer. Am J Transl Res, 1: 148–162, 2009.
8.
PuccettiL., SupuranC.T., FasoloP.P., ContiE., SebastianiG., LacquanitiS., MandrasR., MilazzoM.G., DoglianiN., De GiuliP., FasolisG.: Skewing towards neuroendocrine phenotype in high grade or high stage androgen-responsive primary prostate cancer. Eur Urol, 48: 215–221, 2005.
9.
AhlgrenG., PedersenK., LundbergS., AusG., HugossonJ., AbrahamssonP.A.: Regressive changes and neuroendocrine differentiation in prostate cancer after neoadjuvant hormonal treatment. Prostate, 42: 274–279, 2000.
10.
JibornT., BjartellA., AbrahamssonP.A.: Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment. Urology, 51: 585–589, 1998.
11.
JinR.J., WangY., MasumoriN., IshiiK., TsukamotoT., ShappellS.B., HaywardS.W., KasperS., MatusikR.J.: NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice. Cancer Res, 64: 5489–5495, 2004.
12.
BurchardtT., BurchardtM., ChenM.W., CaoY., de la TailleA., ShabsighA., HayekO., DoraiT., ButtyanR.: Transdifferentiation of prostate cancer cells to a neuroendocrine cell phenotype in vitro and in vivo. J Urol, 162: 1800–1805, 1999.
13.
VisakorpiT., HyytinenE., KoivistoP., TannerM., KeinänenR., PalmbergC., PalotieA., TammelaT., IsolaJ., KallioniemiO.P.: In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet, 9: 401–406, 1995.
14.
TaplinM.E., BubleyG.J., ShusterT.D., FrantzM.E., SpoonerA.E., OgataG.K., KeerH.N., BalkS.P.: Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med, 332: 1393–1398, 1995.
15.
StanbroughM., BubleyG.J., RossK., GolubT.R., RubinM.A., PenningT.M., FebboP.G., BalkS.P.: Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res, 66: 2815–2825, 2006.
16.
ChenC.D., WelsbieD.S., TranC., BaekS.H., ChenR., VessellaR., RosenfeldM.G., SawyersC.L.: Molecular determinants of resistance to antiandrogen therapy. Nat Med, 10: 33–39, 2004.
17.
BonkhoffH., SteinU., RembergerK.: Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. Hum Pathol, 26: 167–170, 1995.
18.
BonkhoffH.: Neuroendocrine cells in benign and malignant prostate tissue: morphogenesis, proliferation, and androgen receptor status. Prostate Suppl, 8: 18–22, 1998.
ChevilleJ.C., TindallD., BoelterC., JenkinsR., LohseC.M., PankratzV.S., SeboT.J., DavisB., BluteM.L.: Metastatic prostate carcinoma to bone: clinical and pathologic features associated with cancer-specific survival. Cancer, 95: 1028–1036, 2002.
21.
CussenotO., VilletteJ.M., Cochand-PriolletB., BerthonP.: Evaluation and clinical value of neuroendocrine differentiation in human prostatic tumors. Prostate Suppl, 8: 43–51, 1998.
