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Prostat kanserinde androjen reseptör yolu inhibitörlerinin uygulanabilirliği: komorbiditeler, yaş ve polifarmasinin etkisi-çok merkezli kohort çalışması

Year 2025, Volume: 8 Issue: 6, 1155 - 1163, 25.10.2025
https://doi.org/10.32322/jhsm.1795533

Abstract

Amaç: Bu çalışmada, prostat kanserinde androjen reseptör yolu inhibitörlerinin (ARPI) komorbidite ve polifarmasi varlığında uygulanabilirliği değerlendirildi.
Yöntem: Yedi merkezden 538 hasta retrospektif olarak incelendi. Tedavi grupları ADT, ARPI ve kemoterapiye göre; ilaç kullanımı ≥3 ve <3 olarak sınıflandırıldı.
Bulgular: Hastaların ortalama yaşı 70,3 yıl olup %59,5’inde komorbidite, %34,4’ünde polifarmasi vardı. ARPI alanlarda sağkalım ADT grubuna göre daha uzundu. Polifarmasi grubunda takip süresi daha uzun ve mortalite daha düşüktü.
Sonuç: ARPI’ler, yaşlı, komorbid ve polifarmasi hastalarında uygulanabilir ve etkilidir.

References

  • Shrestha S, Shrestha S, Khanal S. Polypharmacy in elderly cancer patients: challenges and the way clinical pharmacists can contribute in resource-limited settings. Aging Med (Milton). 2019;2(1):42-49. doi:10. 1002/agm2.12051
  • Kardas P, Lichwierowicz A, Urbański F, Chudzyńska E, Czech M, Kardas G. Prevalence of chronic polypharmacy in community-dwelling elderly people in poland: analysis of national real-world database helps to identify high risk group. Front Pharmacol. 2021;12:739740. doi:10. 3389/fphar 2021.739740.
  • Albertsen PC, Moore DF, Shih W, Lin Y, Li H, Lu-Yao GL. Impact of comorbidity on survival among men with localized prostate cancer. J Clin Oncol. 2011;29(10):1335-1341. doi:10.1200/JCO.2010.31.2330
  • Prathap R, Kirubha S, Rajan AT, Manoharan S, Elumalai K. The increasing prevalence of cancer in the elderly: an investigation of epidemiological trends. Aging Med (Milton). 2024;7(4):516-527. doi:10. 1002/agm2.12347
  • Feng X, Higa GM, Safarudin F, Sambamoorthi U, Tan X. Potentially inappropriate medication use and associated healthcare utilization and costs among older adults with colorectal, breast, and prostate cancers. J Geriatr Oncol. 2019;10(5):698-704. doi:10.1016/j.jgo.2019.01.012
  • Nieder C, Mannsăker B, Pawinski A, Haukland E. Polypharmacy in older patients ≥70 years receiving palliative radiotherapy. Anticancer Res. 2017;37(2):795-799. doi:10.21873/anticanres.11379
  • Saad F, Hamilou Z, Lattouf JB. A drug safety evaluation of enzalutamide to treat advanced prostate cancer. Expert Opin Drug Saf. 2021;20(7):741-749. doi:10.1080/14740338.2021.1919620
  • Lin YT, Huang YC, Liu CK, Lee TS, Chen M, Chien YN. Treatment-emergent co-morbidities and survival in patients with metastatic castration-resistant prostate cancer receiving abiraterone or enzalutamide. Front Pharmacol. 2021;12:669236. doi:10.3389/fphar 2021.669236
  • Shaver AL, Nikita N, Sharma S, et al. The safety of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: an individual-participant data meta-analysis based on 14 randomized clinical trials. Cancers (Basel). 2025;17(17):2747. doi:10.3390/cancers 17172747
  • Shen J, Chowdhury S, Agarwal N, et al. Apalutamide efficacy, safety, and wellbeing in older patients with advanced prostate cancer from phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024; 130(1):73-81. doi:10.1038/s41416-023-02492-8
  • Raval AD, Chen S, Littleton N, Constantinovici N, Goebell PJ. Real-world use of androgen-deprivation therapy intensification for metastatic hormone-sensitive prostate cancer: a systematic review. BJU Int. 2025;135(3):408-421. doi:10.1111/bju.16577
  • Mir N, Burke O, Yates S, et al. Androgen receptor pathway inhibitors, prostate cancer, and older adults: a global Young International Society of Geriatric Oncology drug review. Ther Adv Med Oncol. 2023;15: 17588359221149887. doi:10.1177/17588359221149887
  • Gaber CE, Okpara E, Abdelaziz AI, et al. Real-world effectiveness and cardiovascular safety of abiraterone versus enzalutamide amongst older patients diagnosed with metastatic castration-resistant prostate cancer. J Geriatr Oncol. 2025;16(2):102148. doi:10.1016/j.jgo.2024.102148
  • Bolek H, Yazgan SC, Yekedüz E, et al. Androgen receptor pathway inhibitors and drug-drug interactions in prostate cancer. ESMO Open. 2024;9(11):103736. doi:10.1016/j.esmoop.2024.103736
  • Roviello G, Cappelletti MR, Zanotti L, et al. Targeting the androgenic pathway in elderly patients with castration-resistant prostate cancer: a meta-analysis of randomized trials. Medicine (Baltimore). 2016;95(43): e4636. doi:10.1097/MD.0000000000004636
  • Graff JN, Baciarello G, Armstrong AJ, et al. Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL. Ann Oncol. 2016;27(2):286-294. doi:10.1093/annonc/mdv542
  • George DJ, Ramaswamy K, Yang H, et al. Real-world overall survival with abiraterone acetate versus enzalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2024;27(4):756-764. doi:10.1038/s41391-024-00816-0
  • Merseburger AS, Dornstauder E, Ohlmann CH, et al. Cardiovascular risks and survival with abiraterone vs enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer in Germany: AVENGER study. Adv Ther. 2025;42(4):1919-1934. doi:10.1007/s12325-025-03132-8
  • Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2): 121-131. doi:10.1056/NEJMoa1903835
  • Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700. doi:10.1016/S1470-2045(19)30082-8
  • Huang WK, Su PJ, Chen CC, et al. Comparative effectiveness and safety of enzalutamide versus abiraterone in patients with metastatic castration-resistant prostate cancer: a nationwide registry-based cohort study from Taiwan. J Cancer Res Clin Oncol. 2025;151(11):284. doi:10. 1007/s00432-025-06335-2
  • La J, Wang L, Corrigan JK, et al. Abiraterone or enzalutamide for patients with metastatic castration-resistant prostate cancer. JAMA Netw Open. 2024;7(8):e2428444. doi:10.1001/jamanetworkopen.2024.28444
  • Bahl A, Sodatonou H, Snjider R, et al. Enzalutamide versus abiraterone acetate in the development of new-onset or worsening type 2 diabetes mellitus in patients with metastatic castration-resistant prostate cancer: EVADE study. World J Urol. 2024;42(1):584. doi:10.1007/s00345-024-05280-y
  • Grace M, Vora T, Estil-Las AA, Arsene C. Severe presentation of de novo type II diabetes in abiraterone and prednisone therapy. Cureus. 2025;17(8):e89841. doi:10.7759/cureus.89841
  • Lee YHA, Hui JMH, Leung CH, et al. Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study. Prostate Cancer Prostatic Dis. 2024;27(4):776-782. doi:10.1038/s41391-023-00757-0

Feasibility of androgen receptor pathway inhibitors in prostate cancer: impact of comorbidities, age, and concomitant medication use-a multicenter cohort study

Year 2025, Volume: 8 Issue: 6, 1155 - 1163, 25.10.2025
https://doi.org/10.32322/jhsm.1795533

Abstract

Aims: Androgen receptor pathway inhibitors (ARPIs) have improved outcomes in advanced prostate cancer. Still, evidence regarding their feasibility in older patients with comorbidities and multiple concomitant medications remains limited, as such populations are often underrepresented in clinical trials.
Methods: This multicenter, retrospective cohort study included 538 prostate cancer patients diagnosed between January 2021 and November 2023 across seven centers in Turkiye. Demographic, clinical, pathological, and treatment data were extracted from institutional records. Patients were stratified by treatment type [androgen deprivation therapy (ADT), androgen receptor pathway inhibitor (ARPI), chemotherapy (CT)] and by the number of medications used (≥ three vs. <3). The primary outcome was overall survival (OS); secondary outcomes included follow-up duration, tumor grade, and metastatic distribution.
Results: The mean age at diagnosis was 70.3 years, and 59.5% of patients had comorbidities. Concomitant medication use of three or more drugs, was observed in 34.4%. Metastatic disease was present in 82.3% of cases, most commonly involving the bone (62.8%). ARPI therapy was administered to 72.7% of patients, ADT alone to 18.6%, and CT to 8.7%. Patients receiving ARPIs had higher comorbidity and concomitant medication rates and more frequent metastases than those receiving ADT. Still, they achieved significantly longer median follow-up (901 vs. 470 days, p<0.001) and prolonged OS. Patients with concomitant medication use of three or more drugs also showed a longer follow-up (1081 vs. 573 days, p<0.001), lower mortality (32.4% vs. 47.3%, p=0.001), and a higher proportion of grade 1 tumors compared with patients using fewer than three medications.
Conclusion: In this large real-world cohort, ARPIs were found to be feasible and effective, even in elderly, comorbid, and medication use of three or more patients, supporting their use beyond traditional trial populations.

References

  • Shrestha S, Shrestha S, Khanal S. Polypharmacy in elderly cancer patients: challenges and the way clinical pharmacists can contribute in resource-limited settings. Aging Med (Milton). 2019;2(1):42-49. doi:10. 1002/agm2.12051
  • Kardas P, Lichwierowicz A, Urbański F, Chudzyńska E, Czech M, Kardas G. Prevalence of chronic polypharmacy in community-dwelling elderly people in poland: analysis of national real-world database helps to identify high risk group. Front Pharmacol. 2021;12:739740. doi:10. 3389/fphar 2021.739740.
  • Albertsen PC, Moore DF, Shih W, Lin Y, Li H, Lu-Yao GL. Impact of comorbidity on survival among men with localized prostate cancer. J Clin Oncol. 2011;29(10):1335-1341. doi:10.1200/JCO.2010.31.2330
  • Prathap R, Kirubha S, Rajan AT, Manoharan S, Elumalai K. The increasing prevalence of cancer in the elderly: an investigation of epidemiological trends. Aging Med (Milton). 2024;7(4):516-527. doi:10. 1002/agm2.12347
  • Feng X, Higa GM, Safarudin F, Sambamoorthi U, Tan X. Potentially inappropriate medication use and associated healthcare utilization and costs among older adults with colorectal, breast, and prostate cancers. J Geriatr Oncol. 2019;10(5):698-704. doi:10.1016/j.jgo.2019.01.012
  • Nieder C, Mannsăker B, Pawinski A, Haukland E. Polypharmacy in older patients ≥70 years receiving palliative radiotherapy. Anticancer Res. 2017;37(2):795-799. doi:10.21873/anticanres.11379
  • Saad F, Hamilou Z, Lattouf JB. A drug safety evaluation of enzalutamide to treat advanced prostate cancer. Expert Opin Drug Saf. 2021;20(7):741-749. doi:10.1080/14740338.2021.1919620
  • Lin YT, Huang YC, Liu CK, Lee TS, Chen M, Chien YN. Treatment-emergent co-morbidities and survival in patients with metastatic castration-resistant prostate cancer receiving abiraterone or enzalutamide. Front Pharmacol. 2021;12:669236. doi:10.3389/fphar 2021.669236
  • Shaver AL, Nikita N, Sharma S, et al. The safety of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: an individual-participant data meta-analysis based on 14 randomized clinical trials. Cancers (Basel). 2025;17(17):2747. doi:10.3390/cancers 17172747
  • Shen J, Chowdhury S, Agarwal N, et al. Apalutamide efficacy, safety, and wellbeing in older patients with advanced prostate cancer from phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024; 130(1):73-81. doi:10.1038/s41416-023-02492-8
  • Raval AD, Chen S, Littleton N, Constantinovici N, Goebell PJ. Real-world use of androgen-deprivation therapy intensification for metastatic hormone-sensitive prostate cancer: a systematic review. BJU Int. 2025;135(3):408-421. doi:10.1111/bju.16577
  • Mir N, Burke O, Yates S, et al. Androgen receptor pathway inhibitors, prostate cancer, and older adults: a global Young International Society of Geriatric Oncology drug review. Ther Adv Med Oncol. 2023;15: 17588359221149887. doi:10.1177/17588359221149887
  • Gaber CE, Okpara E, Abdelaziz AI, et al. Real-world effectiveness and cardiovascular safety of abiraterone versus enzalutamide amongst older patients diagnosed with metastatic castration-resistant prostate cancer. J Geriatr Oncol. 2025;16(2):102148. doi:10.1016/j.jgo.2024.102148
  • Bolek H, Yazgan SC, Yekedüz E, et al. Androgen receptor pathway inhibitors and drug-drug interactions in prostate cancer. ESMO Open. 2024;9(11):103736. doi:10.1016/j.esmoop.2024.103736
  • Roviello G, Cappelletti MR, Zanotti L, et al. Targeting the androgenic pathway in elderly patients with castration-resistant prostate cancer: a meta-analysis of randomized trials. Medicine (Baltimore). 2016;95(43): e4636. doi:10.1097/MD.0000000000004636
  • Graff JN, Baciarello G, Armstrong AJ, et al. Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL. Ann Oncol. 2016;27(2):286-294. doi:10.1093/annonc/mdv542
  • George DJ, Ramaswamy K, Yang H, et al. Real-world overall survival with abiraterone acetate versus enzalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2024;27(4):756-764. doi:10.1038/s41391-024-00816-0
  • Merseburger AS, Dornstauder E, Ohlmann CH, et al. Cardiovascular risks and survival with abiraterone vs enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer in Germany: AVENGER study. Adv Ther. 2025;42(4):1919-1934. doi:10.1007/s12325-025-03132-8
  • Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2): 121-131. doi:10.1056/NEJMoa1903835
  • Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700. doi:10.1016/S1470-2045(19)30082-8
  • Huang WK, Su PJ, Chen CC, et al. Comparative effectiveness and safety of enzalutamide versus abiraterone in patients with metastatic castration-resistant prostate cancer: a nationwide registry-based cohort study from Taiwan. J Cancer Res Clin Oncol. 2025;151(11):284. doi:10. 1007/s00432-025-06335-2
  • La J, Wang L, Corrigan JK, et al. Abiraterone or enzalutamide for patients with metastatic castration-resistant prostate cancer. JAMA Netw Open. 2024;7(8):e2428444. doi:10.1001/jamanetworkopen.2024.28444
  • Bahl A, Sodatonou H, Snjider R, et al. Enzalutamide versus abiraterone acetate in the development of new-onset or worsening type 2 diabetes mellitus in patients with metastatic castration-resistant prostate cancer: EVADE study. World J Urol. 2024;42(1):584. doi:10.1007/s00345-024-05280-y
  • Grace M, Vora T, Estil-Las AA, Arsene C. Severe presentation of de novo type II diabetes in abiraterone and prednisone therapy. Cureus. 2025;17(8):e89841. doi:10.7759/cureus.89841
  • Lee YHA, Hui JMH, Leung CH, et al. Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study. Prostate Cancer Prostatic Dis. 2024;27(4):776-782. doi:10.1038/s41391-023-00757-0
There are 25 citations in total.

Details

Primary Language English
Subjects Clinical Oncology
Journal Section Original Article
Authors

Nurullah İlhan 0000-0001-9908-9284

Akif Doğan 0000-0003-4275-2414

Erdem Çubukçu 0000-0002-0070-0889

İlhan Hacıbekiroğlu 0000-0002-0333-7405

Murat Araz 0000-0002-4632-9501

Hacı Mehmet Türk 0000-0003-2206-8148

Mehmet Beşiroğlu 0000-0002-1171-8320

İlker Nihat Ökten 0000-0003-2360-3392

Süleyman Baş 0000-0002-5883-445X

Alpaslan Tanoğlu 0000-0002-7477-6640

Mahmut Gümüş 0000-0003-3550-9993

Publication Date October 25, 2025
Submission Date October 2, 2025
Acceptance Date October 16, 2025
Published in Issue Year 2025 Volume: 8 Issue: 6

Cite

AMA İlhan N, Doğan A, Çubukçu E, et al. Feasibility of androgen receptor pathway inhibitors in prostate cancer: impact of comorbidities, age, and concomitant medication use-a multicenter cohort study. J Health Sci Med / JHSM. October 2025;8(6):1155-1163. doi:10.32322/jhsm.1795533

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