1.A case of flutamide-induced acute cholestatic hepatitis: a case report.
Hong Woo LEE ; Jun Pyo CHUNG ; Kwi Soon LEE ; Kyung Chul KIM ; Kwan Sik LEE ; Chae Yoon CHON ; In Suh PARK ; Ho Geun KIM
Yonsei Medical Journal 1996;37(3):225-229
Flutamide, an oral nonsteroidal, antiandrogenic, anilid compound which inhibits the uptake and binding of androgens to nuclear receptors in the prostate, is used with or without LH-RH analogues for treatment of patients with metastatic carcinoma of the prostate. Clinically significant hepatotoxicities such as toxic hepatitis, cholestatic hepatitis, hepatic failure, and even death have rarely been reported in the English literature, but no case has been reported in Korea. A 75-year-old man with metastatic carcinoma of the prostate had taken flutamide (750 mg/day) for 7 months and suddenly developed jaundice and general weakness. The findings of blood chemistries were compatible with cholestatic hepatitis, but ultrasonography, viral marker and auto-antibody studies did not reveal any attributable causes. Histologic examination of a sono-guided liver biopsy only disclosed centrilobular cholestasis, nuclear glycogenosis and mild sinusoidal lymphocytic infiltration. Discontinuation of flutamide resulted in an almost full recovery of the patient's liver function in 2 months. We, herein, report a case of flutamide-induced acute choestatic hepatitis with a brief review of the literature.
Acute Disease
;
Aged
;
Androgen Antagonists/*adverse effects
;
Case Report
;
Cholestasis/*chemically induced
;
Flutamide/*adverse effects
;
Hepatitis, Toxic/*etiology
;
Human
;
Male
2.Metabolic disorder after androgen deprivation therapy in patients with prostate cancer.
Jia-qi YUAN ; Xiao-wei ZHANG ; Tao XU ; Xiao-feng WANG
Acta Academiae Medicinae Sinicae 2011;33(4):468-472
The prevalence of prostate cancer, a common malignancy of urinary system in elderly males, has increased rapidly in China in recent years. Currently most prostate cancer patients are treated with androgen deprivation therapy (ADT). However, ADT-induced metabolic disorders such as metabolic syndrome has remarkably impaired the quality of life and decreased the survival rate.
Androgen Antagonists
;
adverse effects
;
therapeutic use
;
Humans
;
Male
;
Metabolic Diseases
;
chemically induced
;
Prostatic Neoplasms
;
drug therapy
;
metabolism
3.Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.
Yuan-Bin HUANG ; Wei-Lin LI ; Man SUN ; Xu DUAN ; Yu-Tong WANG ; Lu-Xin ZHANG ; Zi-Han XIN ; Zhi-Fei YUN ; Bo FAN ; Xian-Cheng LI
Asian Journal of Andrology 2023;25(3):366-374
Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.
Male
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Humans
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Prostatic Neoplasms/chemically induced*
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Androgen Antagonists/adverse effects*
;
COVID-19
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Androgens/therapeutic use*
;
SARS-CoV-2
4.Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial.
Byung Ha CHUNG ; Jian HUANG ; Zhang-Qun YE ; Da-Lin HE ; Hirotsugu UEMURA ; Gaku ARAI ; Choung Soo KIM ; Yuan-Yuan ZHANG ; Yusoke KOROKI ; SuYeon JEONG ; Suneel MUNDLE ; Spyros TRIANTOS ; Sharon MCCARTHY ; Kim N CHI ; Ding-Wei YE
Asian Journal of Andrology 2022;24(2):161-166
Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
Androgen Antagonists/adverse effects*
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Exanthema/chemically induced*
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Far East
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Humans
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Male
;
Prostate-Specific Antigen
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Prostatic Neoplasms, Castration-Resistant/pathology*
;
Thiohydantoins/adverse effects*
5.Metabolic complications of androgen deprivation therapy and its intervention management.
Yong-Hui HU ; Song WU ; Meng ZHANG
National Journal of Andrology 2018;24(3):277-281
Androgen deprivation therapy (ADT) is one of the dominant treatment options for advanced prostate cancer, which has been certified to significantly improve the overall survival of prostate cancer patients. However, it sometimes can also produce severe adverse effects on body metabolism. This review summarizes the adverse effects of ADT on body composition, the levels of cholesterol and blood glucose, and the cardiovascular system, and the intervention management of these metabolic complications as well.
Androgen Antagonists
;
adverse effects
;
Blood Glucose
;
drug effects
;
Body Composition
;
drug effects
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Cardiovascular System
;
drug effects
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Cholesterol
;
blood
;
Humans
;
Male
;
Prostatic Neoplasms
;
blood
;
drug therapy
6.Anemia in patients on combined androgen block therapy for prostate cancer.
Li-xin HUA ; Hong-fei WU ; Yuan-geng SUI ; Shuang-guan CHENG ; Zheng-quan XU ; Wei ZHANG
Chinese Journal of Oncology 2003;25(5):496-497
OBJECTIVETo study the effect of combined androgen block therapy on hemoglobin (Hb) and hematocrit value (Ht) in patients with prostate cancer.
METHODSOne hundred and thirty-six patients with adenocarcinoma of the prostate were treated with combined androgen block (orchiectomy and flutamide 250 mg, Tid). Complete blood counts were detected before initiation and after 1, 2, 3, 6, 9 and 12 months of therapy.
RESULTSHb level declined significantly in all patients from a mean baseline of (136 +/- 14) g/L to (126 +/- 16) g/L, (121 +/- 14) g/L, (120 +/- 15) g/L, (113 +/- 12) g/L, (121 +/- 13) g/L and (123 +/- 15) g/L at 1, 2, 3, 6, 9 and 12 months. Ht decreased from a mean baseline of 0.424 +/- 0.041 to 0.390 +/- 0.038, 0.381 +/- 0.042, 0.378 +/- 0.038, 0.366 +/- 0.041, 0.384 +/- 0.039 and 0.387 +/- 0.040. The differences between Hb, Ht before and after treatment were significant (P < 0.05).
CONCLUSIONPatients with prostate cancer being treated with combined androgen block would develop a significant degree of anemia. Hemoglobin and hematocrit level should be monitored periodically. This kind of anemia can be treated by recombinant human erythropoietin.
Aged ; Aged, 80 and over ; Androgen Antagonists ; adverse effects ; Anemia ; chemically induced ; Hematocrit ; Hemoglobins ; analysis ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms ; blood ; drug therapy
7.Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localized prostate cancer (T1-2): a retrospective study.
Rupesh RAINA ; Geetu PAHALAJANI ; Ashok AGARWAL ; Craig ZIPPE
Asian Journal of Andrology 2007;9(2):253-258
AIMTo evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution.
METHODSNinety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d. and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years.
RESULTSThe mean follow-up time was (50.8 +/- 8.5) months in group 1 and (43.1 +/- 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50%) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so.
CONCLUSIONUnlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.
Aged ; Aged, 80 and over ; Androgen Antagonists ; adverse effects ; therapeutic use ; Anilides ; adverse effects ; therapeutic use ; Flutamide ; adverse effects ; therapeutic use ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Imidazolidines ; adverse effects ; therapeutic use ; Leuprolide ; adverse effects ; therapeutic use ; Male ; Nitriles ; adverse effects ; therapeutic use ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; drug therapy ; Retrospective Studies ; Tosyl Compounds ; adverse effects ; therapeutic use
8.Intermittent, low-dose, antiandrogen monotherapy as an alternative therapeutic option for patients with positive surgical margins after radical prostatectomy.
Kyung Hwa CHOI ; Seung Ryeol LEE ; Young Kwon HONG ; Dong Soo PARK
Asian Journal of Andrology 2018;20(3):270-275
The aim of the present study was to determine whether oncologic outcomes and adverse events associated with active on/off intermittent antiandrogen monotherapy (daily bicalutamide, 50 mg per day) are comparable with those of standard external beam radiation therapy (EBRT) or combined androgen blockade (CAB) therapy in prostate cancers with positive surgical margins after radical prostatectomy. Two hundred twenty-three patients with positive surgical margins post-radical prostatectomy who underwent active surveillance (AS, n = 32), EBRT without hormone therapy (n = 55), intermittent antiandrogen monotherapy without EBRT (IAAM, n = 50), or CAB without EBRT (n = 86), between 2007 and 2014, were reviewed retrospectively. Pathologic outcomes, biochemical recurrence rates, radiological disease progression, and adverse events were collected from medical records. Biochemical recurrence rates, biochemical recurrence-free survival rates, and radiological recurrence were not different between the groups (P = 0.225, 0.896, and 0.284, respectively). Adverse event rates and severities were lower for IAAM compared with EBRT or CAB (both P < 0.05), but were comparable to those for AS (P = 0.591 and 0.990, respectively). Grade ≥3 adverse events were not reported in the IAAM or AS groups. Erectile dysfunction and loss of libido rates were lower in the IAAM group compared with the EBRT and CAB groups (P = 0.032). Gastrointestinal complications were more frequently reported in the EBRT group (P = 0.008). Active on/off IAAM treatment might be an appropriate treatment option for patients with positive surgical margins after radical prostatectomy. Furthermore, regarding oncologic outcomes, IAAM was comparable to standard EBRT but had a milder adverse event profile.
Aged
;
Aged, 80 and over
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Androgen Antagonists/adverse effects*
;
Anilides/adverse effects*
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Antineoplastic Agents/adverse effects*
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Chemotherapy, Adjuvant/adverse effects*
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Disease-Free Survival
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Humans
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Male
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Neoplasm Recurrence, Local/blood*
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Neoplasm, Residual
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Nitriles/adverse effects*
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Prostate-Specific Antigen/blood*
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Prostatectomy
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Prostatic Neoplasms/therapy*
;
Radiotherapy, Adjuvant/adverse effects*
;
Retrospective Studies
;
Tosyl Compounds/adverse effects*
9.Worsening of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in patients with prostate cancer after androgen deprivation therapy.
Ryo OKA ; Takanobu UTSUMI ; Takumi ENDO ; Masashi YANO ; Shuichi KAMIJIMA ; Naoto KAMIYA ; Hiroyoshi SUZUKI
Asian Journal of Andrology 2018;20(6):634-636
Aged
;
Androgen Antagonists/adverse effects*
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Anticholesteremic Agents/therapeutic use*
;
Cholesterol, HDL/blood*
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Cholesterol, LDL/blood*
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Humans
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Hypercholesterolemia/chemically induced*
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Lipids/blood*
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Male
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Middle Aged
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Prostatic Neoplasms/therapy*
;
Retrospective Studies
;
Testosterone/blood*
10.Risks of diabetes mellitus and impaired glucose tolerance induced by intermittent versus continuous androgen-deprivation therapy for advanced prostate cancer.
Sheng ZENG ; Zhuo-Ping LI ; Wei LI ; Wei-Zhen PU ; Peng LIU ; Zhi-Fang MA
National Journal of Andrology 2017;23(7):598-602
Objective:
To investigate the correlation of intermittent androgen-deprivation therapy (IADT) and continuous androgen-deprivation therapy (CADT) for advanced prostate cancer (PCa) with the risks of secondary diabetes mellitus (DM) and impaired glucose tolerance (IGT).
METHODS:
We conducted a retrospective case-control study of the advanced PCa patients treated by IADT or CADT in our hospital from January 2013 to December 2015. Based on the levels fasting blood glucose and 2-hour postprandial blood glucose, results of oral glucose tolerance test, and clinical symptoms of the patients, we statistically analyzed the IADT- or CADT-related risk factors for DM and IGT and the relationship of the body mass index (BMI), hypertension, smoking, and alcohol consumption with secondary DM and IGT.
RESULTS:
IADT was given to 53 (46.5%) of the patients, aged (69.1 ± 4.3) years, and CADT to 61 (53.5%), aged (70.2 ± 5.7) years. No statistically significant differences were observed in clinical characteristics between the two groups of patients (P > 0.05). BMI, blood pressure, smoking and drinking exhibited no significant influence on the development of DM or IGT either in the IADT (P > 0.05) or the CADT group. The incidence of IGT was significantly lower in the IADT than in the CADT group (P = 0.03), but that of DM showed no statistically significant difference between the two groups (P = 0.64).
CONCLUSIONS
Compared with CADT, IADT has a lower risk of IGT and a higher safety in the treatment of advanced prostate cancer.
Aged
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Alcohol Drinking
;
adverse effects
;
Androgen Antagonists
;
adverse effects
;
therapeutic use
;
Blood Glucose
;
metabolism
;
Body Mass Index
;
Case-Control Studies
;
Diabetes Mellitus
;
chemically induced
;
Glucose Intolerance
;
chemically induced
;
Glucose Tolerance Test
;
Humans
;
Hypertension
;
complications
;
Male
;
Prostatic Neoplasms
;
drug therapy
;
pathology
;
Retrospective Studies
;
Risk Factors
;
Smoking
;
adverse effects