Corticosteroids alleviate adverse events associated with enzalutamide in patients with metastatic castration‑resistant prostate cancer

Tamura,Keita; Matsushita,Yuto; Watanabe,Hiromitsu; Motoyama,Daisuke; Ito,Toshiki; Sugiyama,Takayuki; Otsuka,Atsushi; Miyake,Hideaki

doi:10.3892/mco.2020.2013

Corticosteroids alleviate adverse events associated with enzalutamide in patients with metastatic castration‑resistant prostate cancer

Authors:
- Keita Tamura
- Yuto Matsushita
- Hiromitsu Watanabe
- Daisuke Motoyama
- Toshiki Ito
- Takayuki Sugiyama
- Atsushi Otsuka
- Hideaki Miyake
View Affiliations

Affiliations: Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431‑3192, Japan
Published online on: March 5, 2020 https://doi.org/10.3892/mco.2020.2013
Pages: 495-500

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the impact of the combined use of corticosteroid on adverse events (AEs) induced by enzalutamide (Enz) in patients with metastatic castration‑resistant prostate cancer (mCRPC). The cohort of the present study included 121 consecutive patients with mCRPC who sequentially received androgen receptor‑axis‑targeted (ARAT) agents, abiraterone acetate (AA) and Enz, in any order, without prior docetaxel therapy. Detailed assessments of AEs during treatment with Enz were conducted according to whether or not corticosteroid was administered. Of these patients, 63 and 58 received ARAT therapy with the Enz‑to‑AA sequence (group 1) and the AA‑to‑Enz sequence (group 2), respectively. No patient in group 1 received corticosteroid during treatment with Enz, while corticosteroid was continuously administered in combination with Enz to all patients in group 2 following AA failure. When ARAT therapy was initiated, no significant differences in the major baseline characteristics were observed between the two groups. During Enz therapy, there were no significant differences in the incidence of any AEs or AEs ≥ grade 3 between the two groups. However, the incidences of fatigue and appetite loss in group 1 were significantly higher when compared with those in group 2. Furthermore, the combined use of corticosteroid was revealed to be independently associated with the prevention of fatigue and appetite loss during Enz therapy. The results of the present study suggested that the combined use of corticosteroids could reduce the incidence of certain types of AE, particularly fatigue and appetite loss, in mCRPC patients treated with Enz.

View Figures

View References

1	Fitzpatrick JM, Bellmunt J, Fizazi K, Heidenreich A, Sternberg CN, Tombal B, Alcaraz A, Bahl A, Bracarda S, Di Lorenzo G, et al: Optimal management of metastatic castration-resistant prostate cancer: Highlights from a European Expert Consensus Panel. Eur J Cancer. 50:1617–1627. 2014.PubMed/NCBI View Article : Google Scholar
2	Chi K, Hotte SJ, Joshua AM, North S, Wyatt AW, Collins LL and Saad F: Treatment of mCRPC in the AR-axis-targeted therapy-resistant state. Ann Oncol. 26:2044–2056. 2015.PubMed/NCBI View Article : Google Scholar
3	Oudard S, Maroto P, Demonty G and Gerritsen WR: Charting recent progress and challenges in metastatic castration-resistant prostate cancer: Is there an optimal treatment sequence? Eur Urol Focus. 2:426–440. 2016.PubMed/NCBI View Article : Google Scholar
4	Ingrosso G, Detti B, Scartoni D, Lancia A, Giacomelli I, Baki M, Carta G, Livi L and Santoni R: Current therapeutic options in metastatic castration-resistant prostate cancer. Semin Oncol. 45:303–315. 2018.PubMed/NCBI View Article : Google Scholar
5	Schalken J and Fitzpatrick JM: Enzalutamide: Targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer. BJU Int. 117:215–225. 2016.PubMed/NCBI View Article : Google Scholar
6	Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, et al: Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 367:1187–1197. 2012.PubMed/NCBI View Article : Google Scholar
7	Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, et al: Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 371:424–433. 2014.PubMed/NCBI View Article : Google Scholar
8	Papazoglou D, Wannesson L, Berthold D, Cathomas R, Gillessen S, Rothermundt C, Hasler L, Winterhalder R, Barth A, Mingrone W, et al: Enzalutamide in patients with castration-resistant prostate cancer progressing after docetaxel: Retrospective analysis of the swiss enzalutamide named patient program. Clin Genitourin Cancer. 15:e315–e323. 2017.PubMed/NCBI View Article : Google Scholar
9	Miyake H, Hara T, Tamura K, Sugiyama T, Furuse H, Ozono S and Fujisawa M: Comparative assessment of efficacies between 2 alternative therapeutic sequences with novel androgen receptor-axis-targeted agents in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 15:e591–e597. 2017.PubMed/NCBI View Article : Google Scholar
10	Thiery-Vuillemin A, Poulsen MH, Lagneau E, Ploussard G, Birtle A, Dourthe LM, Beal-Ardisson D, Pintus E, Trepiakas R, Antoni L, et al: Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and cognition in patients with metastatic castration-resistant prostate cancer: Initial results from the observational AQUARiUS study. ESMO Open. 3(e000397)2018.PubMed/NCBI View Article : Google Scholar
11	Khalaf DJ, Sunderland K, Eigl BJ, Kollmannsberger CK, Ivanov N, Finch DL, Oja C, Vergidis J, Zulfiqar M, Gleave ME and Chi KN: Health-related quality of life for abiraterone plus prednisone versus enzalutamide in patients with metastatic castration-resistant prostate cancer: Results from a phase II randomized trial. Eur Urol. 75:940–947. 2019.PubMed/NCBI View Article : Google Scholar
12	de Bono JS, Chowdhury S, Feyerabend S, Elliott T, Grande E, Melhem-Bertrandt A, Baron B, Hirmand M, Werbrouck P and Fizazi K: Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate plus prednisone for ≥24 weeks in Europe. Eur Urol. 74:37–45. 2018.PubMed/NCBI View Article : Google Scholar
13	Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, et al: Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 368:138–148. 2013.PubMed/NCBI View Article : Google Scholar
14	Dearden L, Shalet N, Artenie C, Mills A, Jackson C, Grant L and Gater A: Fatigue, treatment satisfaction and health-related quality of life among patients receiving novel drugs suppressing androgen signalling for the treatment of metastatic castrate-resistant prostate cancer. Eur J Cancer Care (Engl). 28(e12949)2019.PubMed/NCBI View Article : Google Scholar
15	Roviello G and Generali D: Is the fatigue an adverse event of the second generation of hormonal therapy? Data from a literature-based meta-analysis. Med Oncol. 35(29)2018.PubMed/NCBI View Article : Google Scholar
16	Minton O, Richardson A, Sharpe M, Hotopf M and Stone P: A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst. 100:1155–1166. 2008.PubMed/NCBI View Article : Google Scholar
17	Yennurajalingam S, Frisbee-Hume S, Palmer JL, Delgado-Guay MO, Bull J, Phan AT, Tannir NM, Litton JK, Reddy A, Hui D, et al: Reduction of cancer-related fatigue with dexamethasone: A double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol. 31:3076–3082. 2013.PubMed/NCBI View Article : Google Scholar
18	Eguchi K, Honda M, Kataoka T, Mukouyama T, Tsuneto S, Sakamoto J, Oba K and Saji S: Efficacy of corticosteroids for cancer-related fatigue: A pilot randomized placebo-controlled trial of advanced cancer patients. Palliat Support Care. 13:1301–1308. 2015.PubMed/NCBI View Article : Google Scholar
19	Langston B, Armes J, Levy A, Tidey E and Ream E: The prevalence and severity of fatigue in men with prostate cancer: A systematic review of the literature. Support Care Cancer. 21:1761–1771. 2013.PubMed/NCBI View Article : Google Scholar
20	Mitchell SA, Beck SL, Hood LE, Moore K and Tanner ER: Putting evidence into practice: Evidence-based interventions for fatigue during and following cancer and its treatment. Clin J Oncol Nurs. 11:99–113. 2007.PubMed/NCBI View Article : Google Scholar
21	Nguyen DP, Li J and Tewari AK: Inflammation and prostate cancer: The role of interleukin 6 (IL-6). BJU Int. 113:986–992. 2014.PubMed/NCBI View Article : Google Scholar
22	Miller AH, Ancoli-Israel S, Bower JE, Capuron L and Irwin MR: Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J Clin Oncol. 26:971–982. 2008.PubMed/NCBI View Article : Google Scholar
23	Schultz NM, Penson DF, Wilson S, Song Y, Yang H, Ramaswamy K and Lowentritt B: Adverse events associated with cumulative corticosteroid use in patients with canstration-resistant prostate cancer: An administrative claims analysis. Drug Saf. 43:23–33. 2020.PubMed/NCBI View Article : Google Scholar
24	Miyake H, Hara T, Terakawa T, Ozono S and Fujisawa M: Comparative assessment of clinical outcomes between abiraterone acetate and enzalutamide in patients with docetaxel-naive metastatic castration-resistant prostate cancer: Experience in real-world clinical practice in Japan. Clin Genitourin Cancer. 15:313–319. 2017.PubMed/NCBI View Article : Google Scholar