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1.
Int. braz. j. urol ; 45(3): 503-513, May-June 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1012320

RESUMO

ABSTRACT Purpose: The purposes of the present study were to evaluate growth rate of nonfunctioning adrenal incidentalomas (AIs) and their development to hormonal hypersecretion on follow-up. Materials and methods: A retrospective study was conducted from the electronic medical records. A total of 314 patients were diagnosed with adrenal tumors between 2000 and 2016. After excluding patients who had overt adrenal endocrine disorders or whose adrenal tumors were clinically diagnosed as metastatic malignancies, we investigated 108 patients with nonfunctioning AIs including characteristics, the treatment, the way of follow-up and pathology. Results: Fifteen patients received immediate adrenalectomy because of the initial tumor size or patient's preference. Pathological examination revealed malignancy in 2 patients. In the remaining 93 patients, radiological examinations were performed periodically. Tumor enlargement of ≥ 1.0cm was observed in 8.6% of the patients who were followed up as nonfunctioning AIs with a median follow-up period of 61.5 months (range: 4-192). Eleven patients underwent adrenalectomy. On the pathological examinations, all of the tumors, which showed a size increase, were diagnosed as benign tumors. Regarding the followed up patients without adrenalectomy, only 2.4% of the patients had tumor enlargement during the prolonged follow-up. Furthermore, none of the patients developed hormonal hypersecretion or clinical signs such as obesity, glucose intolerance or poorly controlled hypertension. Conclusions: Tumor enlargement of AIs did not correlate with malignancy. The value of repeat radiological and hormonal examinations may be limited in the long-term follow-up of patients whose AIs are not enlarged.

2.
Intern Med ; 58(16): 2401-2406, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30996194

RESUMO

A 56-year-old man was referred to our facility after developing edema in his right leg. Enhanced computed tomography (CT) revealed a periarterial soft tissue mass surrounding the right iliac artery compressing the iliac vein. His elevated serum IgG4 level indicated IgG4-related disease (IgG4-RD). Both a percutaneous and surgical biopsy of this periarterial lesion proved challenging and were not pursued. A prostate biopsy, however, finally provided a histological diagnosis of IgG4-RD. Oral steroid therapy successfully resolved his leg edema and periarterial lesion. This case illustrates the usefulness of an alternative prostate biopsy for the histological diagnosis of IgG4-RD when approaching the primary affected lesion is difficult.

3.
J Med Case Rep ; 13(1): 98, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31006385

RESUMO

BACKGROUND: There is no established treatment after failure of proven therapies for patients with metastatic renal cell carcinoma. CASE PRESENTATION: A 66-year-old Japanese man with metastatic renal cell carcinoma became refractory to interferon α and sunitinib therapies. He started treatment with axitinib at 10 mg/day, and the dose was gradually tapered down to 4 mg/day because of intolerable adverse events. His metastatic lesions shrank; however, he could not continue due to the adverse events. He started fourth-line therapy with nivolumab; however, the metastatic lesions increased. Rechallenge with axitinib 4 mg/day was started, and the dose was reduced to 2 mg/day because of adverse events. Subsequently, the adverse events became controllable, and the metastatic lesions were maintained at reduced size. CONCLUSION: Therapeutic drug monitoring of axitinib could play an important role in the development of safe and effective therapeutic treatment and individualization of these medications.


Assuntos
Antineoplásicos/administração & dosagem , Axitinibe/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Axitinibe/efeitos adversos , Carcinoma de Células Renais/diagnóstico , Monitoramento de Medicamentos/métodos , Humanos , Interferon-alfa/uso terapêutico , Neoplasias Renais/diagnóstico , Masculino , Invasividade Neoplásica , Nivolumabe/uso terapêutico , Sunitinibe/uso terapêutico
4.
Int Braz J Urol ; 45(3): 503-513, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785700

RESUMO

PURPOSE: The purposes of the present study were to evaluate growth rate of nonfunctioning adrenal incidentalomas (AIs) and their development to hormonal hypersecretion on follow-up. MATERIALS AND METHODS: A retrospective study was conducted from the electronic medical records. A total of 314 patients were diagnosed with adrenal tumors between 2000 and 2016. After excluding patients who had overt adrenal endocrine disorders or whose adrenal tumors were clinically diagnosed as metastatic malignancies, we investigated 108 patients with nonfunctioning AIs including characteristics, the treatment, the way of follow-up and pathology. RESULTS: Fifteen patients received immediate adrenalectomy because of the initial tumor size or patient's preference. Pathological examination revealed malignancy in 2 patients. In the remaining 93 patients, radiological examinations were performed periodically. Tumor enlargement of ≥ 1.0cm was observed in 8.6% of the patients who were followed up as nonfunctioning AIs with a median follow-up period of 61.5 months (range: 4-192). Eleven patients underwent adrenalectomy. On the pathological examinations, all of the tumors, which showed a size increase, were diagnosed as benign tumors. Regarding the followed up patients without adrenalectomy, only 2.4% of the patients had tumor enlargement during the prolonged follow-up. Furthermore, none of the patients developed hormonal hypersecretion or clinical signs such as obesity, glucose intolerance or poorly controlled hypertension. CONCLUSIONS: Tumor enlargement of AIs did not correlate with malignancy. The value of repeat radiological and hormonal examinations may be limited in the long-term follow-up of patients whose AIs are not enlarged.


Assuntos
Corticosteroides/sangue , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Adrenalectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Tomografia Computadorizada por Raios X , Carga Tumoral
7.
Prostate ; 78(3): 222-232, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29194690

RESUMO

BACKGROUND: Clarifying the mechanisms underlying prostate cancer (PC) progression and resistance to androgen deprivation therapy (ADT) is an urgent clinical issue. ADT influences steroidal metabolism in patients with PC and promotes the accumulation of carbon 21 steroids (C21s), such as progestin. Because the enzymes responsible for C21s metabolism are similar to those for androgen metabolism, PC cells may be able to metabolize C21s intracellularly. Therefore, there is a possibility that intracrine C21s are implicated in PC progression and resistance to ADT, and the influence of C21s on PC cells is yet to be elucidated. In the present study, we focused on 20ß-hydroxy-5α-dihydroprogesterone (20ß-OHDHP), a C21s metabolized from progestin, and showed that 20ß-OHDHP is synthesized in PC cells and is able to directly stimulate the androgen receptor (AR). METHODS: LNCaP, VCaP, and DU145 cells, which express a mutant AR (mAR), wild-type AR (wAR), and glucocorticoid receptor (GR), respectively, were incubated in the presence of several agents. After incubation, cell growth was determined by the MTS assay. PSA levels were determined by an enzyme immunoassay, and C21s and androgen levels were measured using liquid chromatography-mass spectrometry. Gene expression was analyzed by quantitative real-time polymerase chain reaction, and steroidal-receptor-related signaling was determined by a reporter assay. RESULTS: We affirmed that 20ß-OHDHP was synthesized from pregnenolone intracellularly in LNCaP and VCaP cells, and 20ß-OHDHP significantly promoted the growth of both cell lines without androgen conversion. 20ß-OHDHP directly stimulated both mAR and wAR. The presence of 20ß-OHDHP was sufficient for the proliferation and survival of LNCaP or VCaP cells, and 20ß-OHDHP promoted cell growth even in the presence of abiraterone. Using DU145 cells, we affirmed that 20ß-OHDHP did not stimulate GR, which has a potential to bypass AR signaling in PC cells promote PC cell growth. CONCLUSIONS: Under ADT, 20ß-OHDHP synthesized intracellularly from accumulated progestin in PC cells may accelerate cell growth via stimulation of both wAR and mAR. This pathway may represent an interesting candidate for targeted therapy.


Assuntos
20-alfa-Di-Hidroprogesterona/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino
9.
J Endourol Case Rep ; 3(1): 13-16, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28265590

RESUMO

A 38-year-old female without the tuberous sclerosis complex was diagnosed with right renal angiomyolipoma of 10 cm in diameter. She underwent laparoscopic retroperitoneal nephron-sparing surgery without renal artery clamping with preoperative selective arterial embolization to avoid a significant risk of hemorrhage and the damage of the renal function during nephron-sparing surgery. The tumor was resected completely. The time taken to complete the procedure was 4 hours 11 minutes and blood loss was 780 mL. She was transfused 400 mL of autologous blood.

10.
Jpn J Clin Oncol ; 47(5): 438-446, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28334771

RESUMO

Objective: To evaluate the efficacy and safety of degarelix 3-month depot in Japanese patients with prostate cancer. Methods: In this Phase II, open-label, parallel-group study, 155 Japanese prostate cancer patients were randomized to treatment with degarelix administered subcutaneously at a maintenance dose of 360 or 480 mg every 84 days for 12 months, after receiving an initial dose of 240 mg. The primary endpoint was the cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28-364). Secondary endpoints included percent change in serum prostate-specific antigen level and proportion of patients with prostate-specific antigen failure at Day 364. For safety, adverse events were evaluated. Results: The cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28-364) was 88.3% (95% confidence interval: 77.9-94.0%) and 97.2% (95% confidence interval: 89.4-99.3%) in the 360 and 480 mg groups, respectively. The median percent change in serum prostate-specific antigen level from baseline to Day 364 was -95.05% and -96.43% in the 360 and 480 mg groups, respectively; the proportion of patients with prostate-specific antigen failure was 2.7% and 1.3%. The most frequent adverse event was injection site reaction; however, this did not cause any patient to discontinue treatment. Conclusions: The 3-month dosing regimen of degarelix 360/480 mg was effective and well tolerated for treatment of Japanese prostate cancer patients. The 480 mg group showed a higher cumulative castration rate than the 360 mg group; thus, 480 mg was considered to be the optimal clinical dosage for future Phase III trials.


Assuntos
Grupo com Ancestrais do Continente Asiático , Quimioterapia de Manutenção , Oligopeptídeos/efeitos adversos , Oligopeptídeos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Relação Dose-Resposta a Droga , Humanos , Masculino , Oligopeptídeos/sangue , Oligopeptídeos/farmacocinética , Neoplasias da Próstata/sangue , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento
11.
Urol Case Rep ; 9: 24-6, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27656416

RESUMO

A 20 years old woman had an external urethral orifice mass and received an excision operation. Seven years later, she complained a tumor with pain that was similar to the previous tumor. She underwent the tumor removal. Pathological diagnosis was a urethral angiomyomatous leiomyoma in the new concept of estrogen receptor-positive smooth muscle tumors.

12.
Sci Rep ; 6: 32198, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27561382

RESUMO

Intratumoural dihydrotestosterone (DHT) synthesis could be an explanation for castration resistance in prostate cancer (PC). By using liquid chromatography-mass spectrometry, we evaluated the intratumoral DHT synthesis from 5α-androstane-3ß,17ß-diol (3ß-diol), which is inactive androgen metabolized from DHT. 3ß-diol had biochemical potential to be converted to DHT via three metabolic pathways and could stimulate PC cell growth. Especially, 3ß-diol was not only converted back to upstream androgens such as dehydroepiandrosterone (DHEA) or Δ5-androstenediol but also converted directly to DHT which is the main pathway from 3ß-diol to DHT. Abiraterone had a significant influence on the metabolism of DHEA, epiandrosterone and 3ß-diol, by the inhibition of the intratumoural 3ß-hydroxysteroid dehydrogenase (3ß-HSD) activities which is one of key catalysts in androgen metabolic pathway. The direct-conversion of 3ß-diol to DHT was catalysed by 3ß-HSD and abiraterone could inhibit this activity of 3ß-HSD. These results suggest that PC had a mechanism of intratumoural androgen metabolism to return inactive androgen to active androgen and intratumoural DHT synthesis from 3ß-diol is important as one of the mechanisms of castration resistance in PC. Additionally, the inhibition of intratumoural 3ß-HSD activity could be a new approach to castration-resistant prostate cancer treatment.


Assuntos
3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Androstano-3,17-diol/metabolismo , Androstenos/farmacologia , Di-Hidrotestosterona/metabolismo , Inibidores Enzimáticos/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias da Próstata/metabolismo , 3-Hidroxiesteroide Desidrogenases/genética , 3-Hidroxiesteroide Desidrogenases/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
14.
Urol Case Rep ; 7: 7-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27335779

RESUMO

Testicular seminoma is a relatively common testicular cancer; however, testicular seminoma with pseudocyst is an extremely rare. The 'burned-out' phenomenon in germ cell tumors refers to a germ cell tumor in extra-gonadal tissues with spontaneous regression of an intra-gonadal tumor. We present a case of the testicular seminoma with pseudocyst and coagulation necrosis like burned-out tumor without metastasis.

15.
BMC Cancer ; 16: 332, 2016 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-27225190

RESUMO

BACKGROUND: Recruitment of cofactors in the interaction of the androgen receptor (AR) and AR ligands plays a critical role in determining androgenic/antiandrogenic effects of the AR ligand on signaling, but the functions of key cofactors, including nuclear receptor coactivator (NCOA), remain poorly understood in prostate cancer cells treated with AR ligands. METHODS: We examined prostate cancer cell lines LNCaP and VCaP expressing mutated and wild-type ARs, respectively, to clarify the significance of NCOAs in the effect of antiandrogens. Hydroxyflutamide showed antagonistic activity against VCaP and an agonistic effect on LNCaP. Bicalutamide served as an antagonist for both. We analyzed mRNA transcription and protein expression of NCOAs in these cells pretreated with dihydrotestosterone and thereafter treated with the mentioned antiandrogens. Transcriptional silencing of candidate NCOAs and AR was performed using small interfering RNA (siRNA). Cell proliferation was evaluated with MTT assay. RESULTS: LNCaP treated with bicalutamide showed an about four-fold increase in the expression of NCOA2 mRNA compared to those pretreated with dihydrotestosterone alone (P <0.01). In VCaP pretreated with dihydrotestosterone, transcriptions of NCOA2 and NCOA7 were slightly increased with bicalutamide (1.96- and 2.42-fold, respectively) and hydroxyflutamide (1.33-fold in both). With Western blotting, the expression of NCOA2 protein also increased in LNCaP cells treated with bicalutamide compared with that in control cells pretreated with dihydrotestosterone alone. Following silencing with siRNA for NCOA2, PSA levels in media with LNCaP receiving bicalutamide were elevated compared with those in non-silencing controls (101.6 ± 4.2 vs. 87.8 ± 1.4 ng/mL, respectively, P =0.0495). In LNCaP cells treated with dihydrotestosterone and bicalutamide, NCOA2-silencing was associated with a higher proliferation activity compared with non-silencing control and AR-silencing. CONCLUSION: NCOA2, which has been thought to be recruited as a coactivator, possibly plays a corepressive role in AR of prostate cancer cells when treated with antiandrogens, suggesting its potential as a therapeutic target.


Assuntos
Antagonistas de Androgênios/farmacologia , Di-Hidrotestosterona/farmacologia , Coativadores de Receptor Nuclear/genética , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/genética , Anilidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Flutamida/análogos & derivados , Flutamida/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Mutação , Nitrilos/farmacologia , Coativadores de Receptor Nuclear/metabolismo , Neoplasias da Próstata/genética , Compostos de Tosil/farmacologia
16.
J Radiat Res ; 57(3): 280-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26983988

RESUMO

We investigated the outcomes of treatment for patients with localized prostate cancer (PCa) treated with 3D conformal radiation therapy (3D-CRT) followed by two-fraction high-dose-rate brachytherapy within a single day (2-fr.-HDR-BT/day) at a single institution. A total of 156 consecutive Asian males (median age, 67 years) were enrolled. To compare our findings with those of other studies, we analyzed our results using the D'Amico classification, assigning the patients to low- ( N =: 5; 3.2%), intermediate- ( N =: 36; 23.1%) and high-risk ( N =: 115; 73.7%) groups (Stage T3 PCa patients were classified as high-risk). One patient in the D'Amico low-risk group (20%), 13 intermediate-risk patients (36.1%) and 99 high-risk patients (86.1%) underwent androgen deprivation therapy. We administered a prescription dose of 39 Gy in 13 fractions of 3D-CRT combined with 18 Gy of HDR-BT in two 9-Gy fractions delivered within a single day. We did not distinguish between risk groups in determining the prescription dose. The median follow-up period was 38 months. Of the 156 patients, one died from primary disease and five died from other diseases. The 3-year overall survival (OS) rates were 100%, 100% and 93.7%, and the 3-year 'biochemical no evidence of disease (bNED)' rates were 100%, 100% and 96.9% for the D'Amico low-, intermediate- and high-risk groups, respectively. No patient developed ≥ Grade 3 early toxicity. The Grade 3 late genitourinary toxicity rate was 2.6%, and no ≥ Grade 3 late gastrointestinal toxicity occurred. The efficacy and safety of this study were satisfactory, and longer-term follow-up is necessary.


Assuntos
Braquiterapia/métodos , Fracionamento da Dose de Radiação , Neoplasias da Próstata/radioterapia , Idoso , Braquiterapia/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Resultado do Tratamento
18.
Jpn J Clin Oncol ; 45(8): 774-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25981621

RESUMO

OBJECTIVE: Abiraterone acetate and docetaxel are promising treatment options for metastatic castration-resistant prostate cancer patients. However, the optimal sequencing of these agents is unclear, and no previous reports discuss Japanese metastatic castration-resistant prostate cancer patients. The purpose of this analysis is to reveal the outcomes of Japanese metastatic castration-resistant prostate cancer patients treated with abiraterone acetate followed by docetaxel. METHODS: We retrospectively reviewed Japanese Phase 1 and Phase 2 trials of metastatic castration-resistant prostate cancer patients treated with abiraterone acetate until disease progression and subsequently treated with docetaxel. The primary outcome measure was the rates of prostate-specific antigen declines ≧30 and ≧50%, respectively, with docetaxel. Secondary outcome measures included progression-free survival with docetaxel, and overall survival after initiation of abiraterone acetate and docetaxel. We performed correlation analysis between previous prostate-specific antigen response to abiraterone acetate and subsequent prostate-specific antigen response to docetaxel. RESULTS: We identified 15 patients had experienced disease progression with abiraterone acetate and subsequently were treated with docetaxel. Prostate-specific antigen declines ≧30 and ≧50% with docetaxel were observed in five patients (33%) and two patients (13%), respectively. The median progression-free survival with docetaxel was 3.7 months (95% confidence interval: 2.9-4.6). The median overall survival from initiation of docetaxel and abiraterone acetate were 14.4 months (95% confidence interval: 6.3-22.4), and 25.7 months (95% confidence interval: 20.1-30.7), respectively. No significant correlation was observed between these prostate-specific antigen responses (Pearson r = 0.206, P = 0.46). CONCLUSION: The efficacy of docetaxel in Japanese mCRPC patients that was resistant to abiraterone acetate was modest. The prostate-specific antigen response to previous abiraterone acetate could not predict the efficacy of subsequent docetaxel. Larger prospective trials are needed to validate these findings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Acetato de Abiraterona , Idoso , Androstenos/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Docetaxel , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do Tratamento
19.
Jpn J Clin Oncol ; 44(12): 1206-15, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25425730

RESUMO

OBJECTIVE: In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. METHODS: Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being docetaxel) for prostate cancer, were enrolled in this open-label, single-arm study. Primary efficacy endpoint was proportion of patients achieving a ≥50% prostate-specific antigen decline from baseline (prostate-specific antigen response rate) after 12-week treatment. Safety and pharmacokinetics were also assessed. RESULTS: Confirmed prostate-specific antigen response rate by Week 12 was 28.3% (90% confidence interval: 17.6%; 41.1%) or 13 out of 46 (full analysis set) treated patients. However, total prostate-specific antigen response rate including confirmed and unconfirmed responses was 34.8% (90% confidence interval: 23.2%; 47.9%). Secondary efficacy endpoints and outcomes were: improvement in Eastern Cooperative Oncology Group performance status score by ≥1 unit: 7/16 patients (43.8%); objective radiographic response: complete response, partial response and stable disease in 0, 1/22 (4.5%) and 9/22 (40.9%) patients, respectively; pain palliation response: 9/16 (56.3%) patients. The most common adverse events (>20% patients) were upper respiratory tract infection (13/47, 27.7% patients) and hepatic function abnormal (10/47, 21.3% patients, Grade 3: 8.5%). All mineralocorticoid-related toxicities were Grade 1/2. CONCLUSIONS: Abiraterone acetate plus prednisolone showed favorable efficacy in metastatic castration-resistant prostate cancer Japanese patients who had received chemotherapy. Abiraterone acetate plus prednisolone had an acceptable safety profile. CLINICAL TRIAL REGISTRATION NO: NCT01795703.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Androstenos/administração & dosagem , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prednisolona/administração & dosagem , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/uso terapêutico
20.
Jpn J Clin Oncol ; 44(12): 1216-26, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25320340

RESUMO

OBJECTIVE: Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated. METHODS: Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed. RESULTS: A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: -66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event >Grade 1/2. CONCLUSIONS: Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. Abiraterone acetate plus prednisolone had an acceptable safety profile. CLINICAL TRIAL REGISTRATION NO: NCT01756638.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona , Idoso , Idoso de 80 Anos ou mais , Androstenos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prednisolona/administração & dosagem , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia
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