Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol

Marie Lange, Heidi Laviec, Hélène Castel, Natacha Heutte, Alexandra Leconte, Isabelle Léger, Bénédicte Giffard, Aurélie Capel, Martine Dubois, Bénédicte Clarisse, Elodie Coquan, Frédéric Di Fiore, Sophie Gouérant, Philippe Bartélémy, Laure Pierard, Karim Fizazi, Florence Joly, Marie Lange, Heidi Laviec, Hélène Castel, Natacha Heutte, Alexandra Leconte, Isabelle Léger, Bénédicte Giffard, Aurélie Capel, Martine Dubois, Bénédicte Clarisse, Elodie Coquan, Frédéric Di Fiore, Sophie Gouérant, Philippe Bartélémy, Laure Pierard, Karim Fizazi, Florence Joly

Abstract

Background: New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for a metastatic CRPCa.

Methods/design: The Cog-Pro study is a multicentre longitudinal study including CRPCa patients ≥70 years old treated with NGHT (n = 134), control metastatic prostate cancer patients without castration resistance treated with first generation androgen deprivation therapy (n = 55), and healthy participants (n = 33), matched on age and education. Cognitive, geriatric and quality of life assessment and biological tests will be performed at baseline, 3, 6 and 12 months after start of the treatment (inclusion time). The primary endpoint is the proportion of elderly patients receiving a NGHT who will experience a decline in cognitive performances within 3 months after study enrollment. Secondary endpoints concern: autonomy, quality of life, anxiety, depression, cognitive reserve, adherence to hormone-therapy, comparison of the cognitive impact of 2 different NGHT (abiraterone acetate and enzalutamide), impact of co-morbidities and biological assessments.

Discussion: Evaluating, understanding and analyzing the incidence, severity of cognitive impairments and their impact on quality of life, autonomy and adherence in this group of patients with advanced disease is a challenge. This study should help to improve cancer care of elderly patients and secure the use of oral treatments as the risk of non-observance does exist. Our results will provide up-to date information for patients and caregivers on impact of these treatments on cognitive function in order to help the physicians in the choice of the treatment.

Trial registration: NCT02907372 , registered: July 26, 2016.

Keywords: Adherence; Ageing; Cognitive impairments; Hormone therapy; Prostate cancer; Quality of life.

Conflict of interest statement

Ethics approval and consent to participate

This study has received ethical approval from the Comité de Protection des Personnes de Nord Ouest III in Avril 2016 and from National Agency for Medical and Health products Safety (Reference: 2016–001248-20). All patients gave their informed consent before any study-related assessment was started.

Consent for publication

Not applicable

Competing interests

FJ received donation from ASTELLAS to conduct this study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flowchart

References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30. doi: 10.3322/caac.21166.
    1. Loriot Y, Massard C, Fizazi K. Recent developments in treatments targeting castration-resistant prostate cancer bone metastases. Ann Oncol. 2012;23(5):1085–1094. doi: 10.1093/annonc/mdr573.
    1. Armstrong AJ. New treatments for men with castration-resistant prostate cancer: can we move from small steps to giant leaps? Eur Urol. 2014;65(2):300–302. doi: 10.1016/j.eururo.2013.08.059.
    1. Lange M, Rigal O, Clarisse B, Giffard B, Sevin E, Barillet M, Eustache F, Joly F. Cognitive dysfunctions in elderly cancer patients: a new challenge for oncologists. Cancer Treat Rev. 2014;40(6):810–817. doi: 10.1016/j.ctrv.2014.03.003.
    1. Lange M, Giffard B, Noal S, Rigal O, Kurtz JE, Heutte N, Levy C, Allouache D, Rieux C, Fel JL, Daireaux A, Clarisse B, Veyret C, Barthelemy P, Longato N, Eustache F, Joly F. Baseline cognitive functions among elderly patients with localised breast cancer. Eur J Cancer. 2014;50:2181–2189. doi: 10.1016/j.ejca.2014.05.026.
    1. Joly F, Giffard B, Rigal O, de Ruiter MB, Small BJ, Dubois M, LeFel J, Schagen SB, Ahles TA, Wefel JS, Vardy JL, Pancre V, Lange M, Castel H. Impact of cancer and its treatments on cognitive function: advances in research from the Paris international cognition and cancer task force symposium and update since 2012. J Pain Symptom Manag. 2015;50(6):830–841. doi: 10.1016/j.jpainsymman.2015.06.019.
    1. Wefel JS, Vardy J, Ahles T, Schagen SB. International cognition and cancer task force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12(7):703–708. doi: 10.1016/S1470-2045(10)70294-1.
    1. Dubois M, Lapinte N, Villier V, Lecointre C, Roy V, Tonon MC, Gandolfo P, Joly F, Hilber P, Castel DH. Chemotherapy-induced long-term alteration of executive functions and hippocampal cell proliferation: role of glucose as adjuvant. Neuropharmacology. 2014;79:234–248. doi: 10.1016/j.neuropharm.2013.11.012.
    1. Lange M, Heutte N, Rigal O, Noal S, Kurtz JE, Levy C, Allouache D, Rieux C, Fel JL, Clarisse B, Veyret C, Barthelemy P, Longato N, Castel H, Eustache F, Giffard B, Joly F. Decline in cognitive functions in elderly early-stage breast cancer patients after adjuvant treatment. Oncologist. 2016;21(11):1337–48.
    1. Nelson CJ, Lee JS, Gamboa MC, Roth AJ. Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer. 2008;113(5):1097–1106. doi: 10.1002/cncr.23658.
    1. McGinty HL, Phillips KM, Jim HS, Cessna JM, Asvat Y, Cases MG, Small BJ, Jacobsen PB. Cognitive functioning in men receiving androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Support Care Cancer. 2014;22(8):2271–2280. doi: 10.1007/s00520-014-2285-1.
    1. Donovan KA, Walker LM, Wassersug RJ, Thompson LM, Robinson JW. Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners. Cancer. 2015;121(24):4286–4299. doi: 10.1002/cncr.29672.
    1. Maggio M, Dall’Aglio E, Lauretani F, Cattabiani C, Ceresini G, Caffarra P, Valenti G, Volpi R, Vignali A, Schiavi G, Ceda GP. The hormonal pathway to cognitive impairment in older men. J Nutr Health Aging. 2012;16(1):40–54. doi: 10.1007/s12603-012-0002-7.
    1. Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. 2002;87(11):5001–5007. doi: 10.1210/jc.2002-020419.
    1. Thilers PP, Macdonald SW, Herlitz A. The association between endogenous free testosterone and cognitive performance: a population-based study in 35 to 90 year-old men and women. Psychoneuroendocrinology. 2006;31(5):565–576. doi: 10.1016/j.psyneuen.2005.12.005.
    1. Young KD, Preskorn SH. Neuroscientific basis of corticosteroid-induced changes in human cognitive and emotional processing: implications for affective illness. J Psychiatr Pract. 2013;19(4):309–315. doi: 10.1097/01.pra.0000432601.09514.12.
    1. Fuller SJ, Tan RS, Martins RN. Androgens in the etiology of Alzheimer’s disease in aging men and possible therapeutic interventions. J Alzheimers Dis. 2007;12(2):129–142. doi: 10.3233/JAD-2007-12202.
    1. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–1197. doi: 10.1056/NEJMoa1207506.
    1. Leranth C, Petnehazy O, MacLusky NJ. Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats. J Neurosci. 2003;23(5):1588–1592.
    1. Hajszan T, MacLusky NJ, Johansen JA, Jordan CL, Leranth C. Effects of androgens and estradiol on spine synapse formation in the prefrontal cortex of normal and testicular feminization mutant male rats. Endocrinology. 2007;148(5):1963–1967. doi: 10.1210/en.2006-1626.
    1. Raskin K, de Gendt K, Duittoz A, Liere P, Verhoeven G, Tronche F, Mhaouty-Kodja S. Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses. J Neurosci. 2009;29(14):4461–4470. doi: 10.1523/JNEUROSCI.0296-09.2009.
    1. Fung C, Dale W, Mohile SG. Prostate cancer in the elderly patient. J Clin Oncol. 2014;32(24):2523–2530. doi: 10.1200/JCO.2014.55.1531.
    1. Agrawal K, Onami S, Mortimer JE, Pal SK. Cognitive changes associated with endocrine therapy for breast cancer. Maturitas. 2010;67(3):209–214. doi: 10.1016/j.maturitas.2010.07.004.
    1. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–699. doi: 10.1111/j.1532-5415.2005.53221.x.
    1. Rey A. Manual of copy and memory reproduction test of complexe geometric figures. Paris: Éditions Centre de psychologie appliquée; 1959.
    1. Herrera-Guzman I, Pena-Casanova J, Lara JP, Gudayol-Ferre E, Bohm P. Influence of age, sex, and education on the visual object and space perception battery (VOSP) in a healthy normal elderly population. Clin Neuropsychol. 2004;18(3):385–394. doi: 10.1080/1385404049052421.
    1. Van der Linden M, Adam S, Agniel A, Ntérion-Thomas C, Baisset-Mouly C, Coyette F, et al. Assessment of memory impairment. Marseille: Solal; 2004.
    1. Baddeley A, Esmlie H, Nimmo-Smith I. The doors and people test. Bury St Edmunds, England: Thames Valley Test Company; 2006.
    1. Wechsler D. [Wechsler Adult Intelligence Scale-III]. Paris: ECPA; 2000.
    1. Reitan R. Validity of trail making tests as an indicator of organic brain damage. Percept Motor Skills. 1958;8:271–276. doi: 10.2466/pms.1958.8.3.271.
    1. Cardebat D, Doyon B, Puel M, Goulet P, Joanette Y. Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level. Acta Neurol Belg. 1990;90(4):207–217.
    1. Moroni C, Bayard S. Inhibitory process: what evolution after the age of 50? Psychol Neuropsychiatr Vieil. 2009;7(1):1–9.
    1. Nelson HE, O’Connell A. Dementia: the estimation of premorbid intelligence levels using the new adult reading test. Cortex. 1978;14(2):234–244. doi: 10.1016/S0010-9452(78)80049-5.
    1. Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P, Brannon J. The functional assessment of cancer therapy scale: development and validation of the general measure. J Clin Oncol. 1993;11(3):570–579. doi: 10.1200/JCO.1993.11.3.570.
    1. Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other anemia-related symptoms with the functional assessment of cancer therapy (FACT) measurement system. J Pain Symptom Manag. 1997;13(2):63–74. doi: 10.1016/S0885-3924(96)00274-6.
    1. Cella D, Nichol MB, Eton D, Nelson JB, Mulani P. Estimating clinically meaningful changes for the functional assessment of cancer therapy-prostate: results from a clinical trial of patients with metastatic hormone-refractory prostate cancer. Value Health. 2009;12(1):124–9.
    1. Joly F, Lange M, Rigal O, Correia H, Giffard B, Beaumont JL, Clisant S, Wagner L. French version of the functional assessment of cancer therapy-cognitive function (FACT-cog) version 3. Support Care Cancer. 2012;20(12):3297–3305. doi: 10.1007/s00520-012-1439-2.
    1. Razavi D, Delvaux N, Farvacques C, Robaye E. Screening for adjustment disorders and major depressive disorders in cancer in-patients. Br J Psychiatry. 1990;156:79–83. doi: 10.1192/bjp.156.1.79.
    1. Gagnon C, Belanger L, Ivers H, Morin CM. Validation of the insomnia severity index in primary care. J Am Board Fam Med. 2013;26(6):701–710. doi: 10.3122/jabfm.2013.06.130064.
    1. Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens (Greenwich ) 2008;10(5):348–354. doi: 10.1111/j.1751-7176.2008.07572.x.
    1. Girerd X, Hanon O, Anagnostopoulos K, Ciupek C, Mourad JJ, Consoli S. Assessment of antihypertensive compliance using a self-administered questionnaire: development and use in a hypertension clinic. Presse Med. 2001;30(21):1044–1048.
    1. Soubeyran P, Bellera C, Goyard J, Heitz D, Cure H, Rousselot H, Albrand G, Servent V, Jean OS, van Praagh I, Kurtz JE, Perin S, Verhaeghe JL, Terret C, Desauw C, Girre V, Mertens C, Mathoulin-Pelissier S, Rainfray M. Screening for vulnerability in older cancer patients: the ONCODAGE prospective multicenter cohort study. PLoS One. 2014;9(12):e115060. doi: 10.1371/journal.pone.0115060.
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. doi: 10.1016/0021-9681(87)90171-8.
    1. Katz S, Downs TD, Cash HR, Grotz RC. Progress in development of the index of ADL. Gerontologist. 1970;10(1):20–30. doi: 10.1093/geront/10.1_Part_1.20.
    1. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–186. doi: 10.1093/geront/9.3_Part_1.179.
    1. Guigoz Y, Vellas B, Garry PJ. Assessing the nutritional status of the elderly: the mini nutritional assessment as part of the geriatric evaluation. Nutr Rev. 1996;54(1 Pt 2):S59–S65.
    1. Podsiadlo D, Richardson S. The timed “up & go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142–148. doi: 10.1111/j.1532-5415.1991.tb01616.x.
    1. Stewart A, Collins B, Mackenzie J, Tomiak E, Verma S, Bielajew C. The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psycho-Oncology. 2008;17(2):122–130. doi: 10.1002/pon.1210.
    1. McSweeney AJ, Naugle RI, Chelune GJ, Lunders H. “T scores for change”: an illustration of a regression approach to depicting change in clinical neuropsychology. Clin Neuropsychol. 1993;7:300–312. doi: 10.1080/13854049308401901.
    1. Sawrie SM, Marson DC, Boothe AL, Harrell LE. A method for assessing clinically relevant individual cognitive change in older adult populations. J Gerontol B Psychol Sci Soc Sci. 1999;54(2):116–124. doi: 10.1093/geronb/54B.2.P116.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren