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1.
Anticancer Res ; 40(4): 2053-2057, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234896

RESUMO

BACKGROUND: The present study aimed to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer. PATIENTS AND METHODS: We investigated 25 patients treated with SBRT of 35 Gy per five fractions from May 2014 to March 2015. RESULTS: The median age of patients was 70 years, four (16%) patients were low risk and 21 (84%) were intermediate risk. Seven (28%) patients received neoadjuvant androgen-deprivation therapy. The median follow-up time was 53 months. Grade 2 acute and late genitourinary toxicities were observed in five (20%) and two (8%) patients and there were no Grade 2 gastrointestinal toxicities. There were no Grade 3 or higher acute or late toxicities at 2 years follow-up. The biochemical relapse-free survival rate at 2 years was 100%. CONCLUSION: SBRT of 35 Gy per five fractions is a promising treatment method in the short term for prostate cancer.


Assuntos
Androgênios/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Neoplasias da Próstata/radioterapia , Radiocirurgia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Fracionamento da Dose de Radiação , Trato Gastrointestinal/patologia , Humanos , Masculino , Terapia Neoadjuvante , Próstata/patologia , Próstata/efeitos da radiação , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Planejamento da Radioterapia Assistida por Computador , Medição de Risco , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(13): e19618, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221087

RESUMO

BACKGROUND: Recently, many endocrine therapies have become available for hormone receptor-positive, human epidermal growth factor receptor 2-negative, pretreated, advanced breast cancer. Direct comparisons of these novel treatments to assess their added value, however, are lacking METHODS:: Our aim was to synthesize available evidence to compare all current endocrine treatments for hormone receptor-positive / human epidermal growth factor receptor 2-negative advanced breast cancer. We performed a systematic review to identify available randomized controlled trial evidence. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Clinical Trials. Two trials presented at international oncology congresses (American Society of Clinical Oncology [ASCO]) were added to include the most recent evidence. A frequent network meta-analysis was used, and the surface under cumulative ranking area (SUCRA) was calculated to determine the best treatment RESULTS:: In total, 32 trials and 12,726 patients were identified, including 27 arms. Compared with fulvestrant 500 mg alone, novel target inhibitors combined with fulvestrant or exemestane had significantly prolonged progression-free survival with hazard ratios ranging from 0.62 to 0.82. Fulvestrant 500 mg plus palbociclib 125 mg and exemestane 25 mg plus entinostat 5 mg similarly extended progression-free survival (hazard ratio: 0.64 and 0.62 with SUCRA values of 91% and 92%, respectively). The exemestane 25 mg plus everolimus 10 mg combination had the best clinical benefit rate (risk ratio: 1.84, SUCRA: 91%) and overall response rate (risk ratio: 6.05, SUCRA: 97%) CONCLUSIONS:: On the basis of this analysis, the 2 combinations of exemestane plus everolimus and fulvestrant plus palbociclib were the best treatment options.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pós-Menopausa , Receptor ErbB-2/biossíntese , Androstadienos/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Everolimo/uso terapêutico , Feminino , Fulvestranto/uso terapêutico , Humanos , Gradação de Tumores , Metanálise em Rede , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Medicine (Baltimore) ; 99(8): e19083, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080081

RESUMO

BACKGROUND: Breast cancer is the most prevalent cancer in females and disease recurrence remains a significant problem. To prevent recurrence, tamoxifen is prescribed for at least 5 years. However, among patients who receive tamoxifen, individual responses are highly variable. These responses are affected by the type, frequency, and severity of endocrine symptoms, as well as adherence rates. Polymorphisms in genes involved in the metabolism of tamoxifen (ie, CYP3A4, CYP2D6) may influence responses to tamoxifen. In this study, the inter-relationships among endocrine symptoms, drug adherence, and genetic polymorphisms in Chinese breast cancer patients receiving tamoxifen therapy will be examined. We hypothesize that patients with more severe endocrine symptoms will be less likely to adhere to tamoxifen treatment. In addition, we hypothesize that a relationship will exist between the severity of tamoxifen-induced symptoms and allelic variations in tamoxifen metabolism-related genes. Although many association studies have determined that select genotypes influence the efficacy of tamoxifen, very few studies have investigated for associations between tamoxifen-induced endocrine symptoms and these polymorphisms. OBJECTIVES: The aim of this study was to characterize genetic polymorphisms in tamoxifen metabolism-associated genes in Chinese women with breast cancer and to explore the inter-relationships between genetic polymorphisms, endocrine symptoms, and adherence to tamoxifen. METHOD: We will conduct a prospective cohort study that follows 200 Chinese women over 18 months and assess treatment-related symptoms and genetic variations. Endocrine symptoms and drug adherence will be determined through interview-administered standardized questionnaires. Polymorphisms in drug metabolism genes will be determined using real-time polymerase chain reaction based genotyping method. Data will be analyzed to determine associations between allelic variations, endocrine symptoms, and adherence. DISCUSSION: The proposed study will evaluate for polymorphisms in gene(s) that are associated with tamoxifen-related endocrine symptoms and adherence with tamoxifen. We will explore the relationships between genotypes, endocrine symptoms, and drug adherence in Chinese breast cancer patients. Findings from this study may assist clinicians to identify patients at higher risk for a worse symptom experience and lower adherence rates and enable them to initiate appropriate interventions. In the long term, the findings from this study may be used to develop and test tailored symptom management interventions for these patients.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Doenças do Sistema Endócrino/induzido quimicamente , Tamoxifeno/efeitos adversos , Alelos , Antineoplásicos Hormonais/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/epidemiologia , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Cooperação do Paciente , Polimorfismo de Nucleotídeo Único , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença , Tamoxifeno/metabolismo , Tamoxifeno/uso terapêutico
4.
Urology ; 137: 84-90, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31877313

RESUMO

OBJECTIVE: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6. MATERIALS AND METHODS: CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed. RESULTS: A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581). CONCLUSION: Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy.


Assuntos
Citocromo P-450 CYP2D6/genética , Qualidade de Vida , Fibrose Retroperitoneal , Tamoxifeno , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos/métodos , Polimorfismo de Nucleotídeo Único , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Fibrose Retroperitoneal/diagnóstico por imagem , Fibrose Retroperitoneal/tratamento farmacológico , Fibrose Retroperitoneal/genética , Fibrose Retroperitoneal/psicologia , Espaço Retroperitoneal/diagnóstico por imagem , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Resultado do Tratamento
5.
Anticancer Res ; 39(11): 6373-6378, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704870

RESUMO

BACKGROUND/AIM: Radiotherapy (RT) with adjuvant hormone therapy (HT) improves prognosis in prostate cancer (PC) patients. Gonadotrophin-releasing hormone agonist (GnRHa) with luteinizing hormone-releasing hormone (LH-RH) analogues is the standard HT. High-dose antiandrogen therapy also improves survival in patients with locally advanced PC. The aim of this study was to compare the results of patients treated with RT plus GnRHa and patients treated with RT plus bicalutamide. PATIENTS AND METHODS: Our institutional PC database was used to identify patients treated with definitive or postoperative RT +/- HT which were included in this study. RESULTS: Three hundred and eighteen patients were retrospectively reviewed (median follow-up=56 months). Five-year biochemical relapse-free survival was 85.5% and 88.3% in patients treated with GnRHa and bicalutamide, respectively (p=0.712). CONCLUSION: Bicalutamide may be offered as an adjuvant treatment to RT in patients who refuse GnRHa because of related side effects. Furthermore, our study justifies randomized trials comparing RT plus GnRHa and RT plus bicalutamide.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Anilidas/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Nitrilos/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Compostos de Tosil/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Anilidas/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Estudos de Casos e Controles , Terapia Combinada/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Prognóstico , Antígeno Prostático Específico/sangue , Estudos Retrospectivos , Compostos de Tosil/efeitos adversos
6.
Medicine (Baltimore) ; 98(43): e17746, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651908

RESUMO

As research progressed, the recommended duration of endocrine therapy for breast cancer patients has been extended from 5 to 10 years. This study aimed to investigate how the duration of endocrine medication and therapy affect survival rate in the real world. By using the National Health Insurance Research Database (NHIRD), this study examined 1002 breast cancer patients newly diagnosed between 2000 and 2005 as research subjects, and conducted follow-up until 2013. Among these subjects, 51 used aromatase inhibitors (AIs), 561 used tamoxifen, and 390 alternated between the use of tamoxifen and AIs. The mean follow-up period in this study was 9.63 years, and the mean duration of taking endocrine medication was 4.04 years. The tamoxifen group had the longest follow-up period (9.87 years), shortest endocrine therapy duration (3.29 years), and best survival rate (86.1%). Patients were divided into 3 groups based on the duration of endocrine therapy: under 2 years, 2 to 5 years, and over 5 years. It was found that patients who received medication for less than 2 years showed the lowest survival rate with statistically significant differences (P < .001). Therefore, the extension of endocrine therapy duration is critical in improving breast cancer patients' survival rate.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan
7.
Breast Cancer Res ; 21(1): 108, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533777

RESUMO

BACKGROUND: The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. METHODS: Postmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. RESULTS: Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (- 73.2%) was numerically higher compared to LTZ (- 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. CONCLUSIONS: Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. TRIAL REGISTRATION: NCT02802748 , registered 16 June 2016.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Vinorelbina/administração & dosagem , Administração Metronômica , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Letrozol/administração & dosagem , Letrozol/efeitos adversos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Pessoa de Meia-Idade , Pós-Menopausa , Receptor ErbB-2/metabolismo , Receptores de Esteroides/metabolismo , Vinorelbina/efeitos adversos
8.
Anticancer Res ; 39(9): 4897-4903, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519593

RESUMO

BACKGROUND/AIM: Endometrial hyperplastic polyps (EHP) may progress to endometrial carcinoma (EC) if left untreated. We aimed to prospectively investigate the efficacy of the low-dose levonorgestrel intrauterine system (LNG-IUS) as therapy for EHP with malignant potential. PATIENTS AND METHODS: In total, 37 women with EHP underwent therapy with LNG-IUS containing 13.5 mg levonorgestrel for six months or 4-10 weeks depending on whether the EHP was characterized (by D-score analysis) as low- to medium-risk (n=33) or high-risk (n=4) of coexistent or future EC. Therapy response was defined as complete clearance of hyperplastic glands in post-therapy endometrial biopsy. RESULTS: All women with low- to medium-risk EHP obtained therapy response, whereas only 1 out of 4 with high-risk EHP responded to therapy. None of the women were diagnosed with EC during the study and no serious adverse events occurred. CONCLUSION: Low-dose LNG-IUS represents a promising therapy for selected women with EHP.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , Pólipos/patologia , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Progestinas/administração & dosagem , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Progestinas/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
9.
Recenti Prog Med ; 110(7): 347-355, 2019.
Artigo em Italiano | MEDLINE | ID: mdl-31379370

RESUMO

LHRH analogues (LHRHa) are used in the treatment of breast cancer that occurs in young women. Amenorrhoea induced by chemotherapy correlates with a reduced risk of recurrence disease. In premenopausal women, analogous LHRHs are used to suppress ovarian estrogen production, raising estrogen hormone levels to post-menopausal values and improving patient outcomes. Two large clinical studies have investigated the role of complete estrogen blockage in adjuvant hormonal treatment of premenopausal patients. Both studies showed the clinical benefit of ovarian suppression treatment, mainly associated with non-steroidal aromatase inhibitor exemestane in high-risk patients. In the recent years, hormonal treatments made available in clinical practice have considerably prolonged the median survival of patients suffering from endocrine-responsive metastatic breast cancer. Even in the premenopausal setting, CDK4/6 inhibitors in association with endocrine therapy have shown a marked improvement in patient outcomes. The safety and efficacy of this new class of drugs demonstrated in the MONALEESA-7 study in premenopausal women and in the premenopausal subgroups of the PALOMA-3 and MONARCH 2 studies support the use of hormone therapy and analogous LHRH combined with CDK 4/6 inhibitor in patients in premenopausal. Finally, LHRH analogues have been extensively studied in strategies for maintaining ovarian function and fertility preservation during adjuvant chemotherapy in younger patients.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Pré-Menopausa , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacologia , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/farmacologia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Feminino , Preservação da Fertilidade , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos
10.
Breast Cancer Res Treat ; 178(2): 419-426, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401686

RESUMO

PURPOSE: To evaluate if real-world utilization of neoadjuvant endocrine therapy (NET) is associated with similar rates of response and breast conservation surgery (BCS) compared to neoadjuvant chemotherapy (NAC). METHODS: Our population-based assessment used the National Cancer Data Base to identify women diagnosed with stage II-III, hormone receptor (HR)-positive BC who underwent surgery and received endocrine therapy from 2004 to 2014. Women were categorized by receipt of NET, NAC or no neoadjuvant therapy. We used logistic regression to assess differences in outcomes between therapies using inverse propensity score weighting to adjust for potential selection bias. RESULTS: In our sample of 211,986 women, 6584 received NET, 52,310 received NAC, and 153,092 did not receive any neoadjuvant therapy. After adjusting for multiple relevant covariates and cofounders, there was no significant difference between NET and NAC with regard to BCS [odds ratio (OR) 0.91; 95% confidence interval (CI) (0.82-1.01)]; however, women who received NET were significantly less likely to achieve pCR [OR 0.34; 95% CI (0.23-0.51)] or a decrease in T stage [OR 0.39; CI (0.34-0.44)] compared to women treated with NAC. Patients who received NET for ≥ 3 months had higher odds of BCS (OR 1.59; 95% CI 1.46-1.73) and downstaging (OR 1.79; 95% CI 1.63-1.97) compared to patients who did not receive neoadjuvant therapy. CONCLUSIONS: Women who received NET had similar rates of BCS compared to women who received NAC. Those who received NET for longer treatment durations had increased odds of BCS and downstaging compared to women who did not receive neoadjuvant therapy.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
EBioMedicine ; 47: 170-183, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31466918

RESUMO

BACKGROUND: Recent clinical trials on ovarian cancer with mifepristone (MF) have failed, despite in vitro findings on its strong progesterone (P4) antagonist function. METHODS: Ovarian cancer human and murine cell lines, cultured high-grade human primary epithelial ovarian cancer (HG-hOEC) cells and their explants; as well as in vivo transgenic mice possessing ovarian cancer were used to assess the molecular mechanism underlying mifepristone (MF) agonistic actions in ovarian cancer progression. FINDINGS: Herein, we show that ovarian cancer cells express traceable/no nuclear P4 receptor (PGR), but abundantly P4 receptor membrane component 1 (PGRMC1). MF significantly stimulated ovarian cancer cell migration, proliferation and growth in vivo, and the translocation of PGRMC1 into the nucleus of cancer cells; the effects inhibited by PGRMC1 inhibitor. The beneficial antitumor effect of high-doses MF could not be achieved in human cancer tissue, and the low tissue concentrations achieved with the therapeutic doses only promoted the growth of ovarian cancers. INTERPRETATION: Our results indicate that treatment of ovarian cancer with MF and P4 may induce similar adverse agonistic effects in the absence of classical nuclear PGRs in ovarian cancer. The blockage of PGRMC1 activity may provide a novel treatment strategy for ovarian cancer. FUND: This work was supported by grants from the National Science Centre, Poland (2013/09/N/NZ5/01831 to DP-T; 2012/05/B/NZ5/01867 to MC), Academy of Finland (254366 to NAR), Moikoinen Cancer Research Foundation (to NAR) and EU PARP Cluster grant (UDA-POIG.05.01.00-005/12-00/NCREMFP to SW).


Assuntos
Antineoplásicos Hormonais/farmacologia , Mifepristona/farmacologia , Animais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacocinética , Biomarcadores , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Mifepristona/administração & dosagem , Mifepristona/farmacocinética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
12.
J Nippon Med Sch ; 86(3): 165-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31292328

RESUMO

BACKGROUND: Fulvestrant 500 mg has been an option for endocrine therapy for advanced or recurrent breast cancer after prior endocrine treatment since November 2011 in Japan. This study aimed to clarify the effectiveness and safety of fulvestrant 500 mg in clinical settings. METHODS: This was a multicenter, both prospective and retrospective, observational study of 132 postmenopausal women (median age 66) with locally advanced or metastatic breast cancer, who had been treated with fulvestrant. Information from medical records was retrospectively obtained from 9 hospitals (Saitama Breast Cancer Clinical Study Group: SBCCSG) in Saitama prefecture, Japan, from October 2012 to April 2014. The primary end point was time to treatment failure (TTF). The secondary end points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AE) (CTCAE ver. 4). The choice of subsequent therapy after fulvestrant was also evaluated. RESULTS: The median TTF was 6.1 months. Median OS was 28.5 months (the starting date was the first day of fulvestrant). ORR was 12.9% and CBR was 45.5%. The most common AEs were injection site reactions (9.1%). The rate of grade 3 AE was only 2.3% (3/132). The number of patients who underwent subsequent therapy after fulvestrant were 54 (55.7%) receiving chemotherapy, 42 (43.3%) receiving non-fulvestrant endocrine therapy, and 1 (1%) receiving mammalian target of rapamycin inhibitor (mTORi) + endocrine therapy (ET). CONCLUSION: Fulvestrant 500 mg is an effective and safe treatment for patients with advanced or recurrent breast cancer after prior endocrine treatment.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Antagonistas do Receptor de Estrogênio/administração & dosagem , Fulvestranto/administração & dosagem , Pós-Menopausa , Receptores Estrogênicos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Estudos de Coortes , Terapia Combinada , Antagonistas do Receptor de Estrogênio/efeitos adversos , Feminino , Fulvestranto/efeitos adversos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
13.
In Vivo ; 33(4): 1381-1392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280234

RESUMO

BACKGROUND/AIM: Anti-cancer therapies may deteriorate cognitive functioning, affective functioning and psychological well-being. MATERIALS AND METHODS: In this prospective longitudinal pilot study, premenopausal and postmenopausal patients received adjuvant endocrine therapy (ET) (tamoxifen with or without LHRH analog or aromatase inhibitor) or were observed only (control group). At baseline testing and 6, 12 and 24 months thereafter, cognitive, depression and anxiety tests and quality of life (QOL) measurements were performed. RESULTS: Overall, 46 cases were evaluated. None of the studied cognitive parameters differed between the subgroups or changed by time. No differences were found regarding anxiety, depression or QOL measures either. Baseline cognitive test and QOL results were in association with later anxiety and depression. CONCLUSION: No cognitive impairment was found during the two years of ET. Baseline cognitive scores and QOL dimensions proved good predictors of later anxiety and depression.


Assuntos
Neoplasias da Mama/psicologia , Cognição , Adulto , Idoso , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/psicologia , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Pós-Menopausa , Pré-Menopausa , Qualidade de Vida
14.
Breast Cancer Res Treat ; 177(3): 549-559, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31270763

RESUMO

PURPOSE: Breast cancer in young Asian women has distinctive clinicopathological characteristics; hence, we question the universal generalizability of treatment recommendations based on data from predominantly non-Asian postmenopausal women. METHODS: The Asian Breast Cancer Cooperative Group (ABCCG) reviewed current ESO-ESMO and St. Gallen recommendations for treating hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer in premenopausal women. Points disputed by ≥ 3/12 members were discussed, and statements on contentious issues formulated for anonymous voting; consensus required a ≥ 75% majority. RESULTS: The ABCCG contends that: (1) Trials in premenopausal women are not only necessary, but also worthwhile if performed separately from others that also enroll postmenopausal participants. (2) Not all premenopausal women with HR+ early breast cancer need adjuvant ovarian function suppression (OFS). (3) Certain clinical factors might influence decision-making about prescribing OFS. (4) For early HR+/HER2- breast cancer in premenopausal patients with OFS, tamoxifen is preferred for intermediate-risk cases; for high risk, near-consensus supported aromatase inhibitor, despite no clear overall survival benefit versus tamoxifen. (5) Oncotype DX Breast Recurrence Score® has different treatment implications in patients aged ≤ 50 versus > 50 years. (6) High-risk patients (if premenopausal after chemotherapy) should receive adjuvant chemotherapy and OFS plus aromatase inhibitor. (7) For patients with advanced disease receiving OFS on a backbone of tamoxifen, gonadotrophin-releasing hormone agonists may be given 12-weekly. (8) For premenopausal women who decline OFS or oophorectomy, tamoxifen alone is still an option but is considered less effective; other monotherapies are also less effective than OFS plus such treatments. CONCLUSION: Premenopausal Asian women with breast cancer have unique disease characteristics and may benefit from treatment that differs somewhat from international guidelines. Given the great diversity of patients and clinical settings worldwide, the ABCCG advocates evidence-based yet flexible and individualized use of all potential options to improve breast cancer outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Fatores Etários , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/diagnóstico , Ensaios Clínicos como Assunto , Feminino , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Pré-Menopausa , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Resultado do Tratamento
15.
AAPS PharmSciTech ; 20(5): 213, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165298

RESUMO

Thermo and pH-responsive poly-N-isopropylacrylamide (PNIPAM) polymer has gained interest due to microenvironment targeting potential toward cancer cells. Its exceptional potential of the phase transition at body temperature (37°C) makes it biologically relevant for drug delivery and biosensing. The optimum drug loading and particle size with controlled release at a specific site are essential for critical process parameters (CPP). This study investigates the formulation optimization anastrozole (ANST)-loaded PNIPAM nanoparticle (NPs) prepared by solvent evaporation method for pH- and thermo-responsive drug delivery. Box-Behnken design (BBD) was implemented to observe the effect of selected process parameters on quality attributes product including particle size 110.15 nm, zeta potential - 11.02 mV, PDI 0.175, and drug loading 8.35% (DL). The statistical data was found to fit in the quadratic model and p value is less than 0.005. The thermo-responsive behavior of PNIPAM is evaluated on DLS and UV-Visible spectroscopy at elevated temperature to 60°C that has shown increment in turbidity showed aggregation of the nanoparticles. The TEM and AFM revealed the spherical and smooth surface ANST-PNIPAM NPs. The formulation showed the controlled release of ANST for 48 h at pH 7.4 and triggered release at simulated tumor microenvironment pH 5.0. The in vitro cytotoxicity of the formulation is higher than free ANST and shown dose-dependent cell viability. The higher cell uptake was observed by NPs after 12-h incubation in MCF-7 cell lines using confocal microscopy. Apoptotic evaluation of ANST-PNIPAM NPs exhibited 22.67% in comparison to free ANST where 6% was analyzed on the flow cytometer.


Assuntos
Resinas Acrílicas/química , Anastrozol/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Concentração de Íons de Hidrogênio , Nanoestruturas/química , Temperatura , Sistemas de Liberação de Medicamentos/métodos , Géis , Humanos , Células MCF-7 , Transição de Fase , Polietilenoimina/química
16.
Breast Cancer Res Treat ; 177(2): 395-399, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172406

RESUMO

PURPOSE: This pilot study evaluated adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging. METHODS: This was a single-arm prospective investigational pilot study that enrolled 86 patients between August 2012 and April 2014. Descriptive statistics for patient age, race, insurance, stage, duration of treatment, and comorbidities were computed. All patients received routine prescriptions in a "bubble" pack or daily blister pack dispensed by one pharmacy. Participants were considered adherent if they had taken ≥ 80% of the dispensed drug. Disease-free survival (DFS) and overall survival (OS) data were obtained at 78 months. RESULTS: Fifty patients were included in the analysis. The overall adherence rate was 97%. None of the variables examined (race, age, insurance status, and stage) had an impact on adherence rate. Only duration of endocrine therapy had a marginal effect on adherence (p value = 0.06). The late cohort (duration of therapy 37-60 months) was least likely to be compliant at 89.53%. Our 5-year DFS was 94% and 5-year OS was 96%. There was no statistically significant difference in DFS and OS between patients with adherence rate > 90% and < 90%. CONCLUSION: Adherence rate to bubble packaging was higher than that in historical studies. Although this is a single-arm pilot study, these data suggest bubble packaging of anti-estrogen may be a reasonable option to improve adherence in hormone receptor-positive breast cancer patients.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Adesão à Medicação , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Resultado do Tratamento
17.
ACS Chem Biol ; 14(7): 1507-1514, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31243955

RESUMO

Chemotherapeutics that self-assemble into colloids have limited efficacy above their critical aggregation concentration due to their inability to penetrate intact plasma membranes. Even when colloid uptake is promoted, issues with colloid escape from the endolysosomal pathway persist. By stabilizing acid-responsive lapatinib colloids through coaggregation with fulvestrant, and inclusion of transferrin, we demonstrate colloid internalization by cancer cells, where subsequent lapatinib ionization leads to endosomal leakage and increased cytotoxicity. These results demonstrate a strategy for triggered drug release from stable colloidal aggregates.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Coloides/química , Preparações de Ação Retardada/química , Fulvestranto/administração & dosagem , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Endossomos/metabolismo , Fulvestranto/farmacocinética , Fulvestranto/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transferrina/química
18.
Int Urol Nephrol ; 51(7): 1113-1119, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31111393

RESUMO

OBJECTIVES: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) patients has been reported to have an association with rheumatoid arthritis. We aimed to assess the impact of ADT on the subsequent risk of tenosynovitis. METHODS: Using data from the National Health Insurance Research Database of Taiwan between 2001 and 2013, 3309 patients with PCa were identified. Among them, 729 ADT patients comprised the study group with 729 matched non-ADT controls. We used a 1:1 propensity score matched analysis. The demographic characteristics and comorbidities of the patients were analyzed; Cox proportional hazards regression was used to calculate the hazard ratios (HR) for the risk of tenosynovitis. RESULTS: There were 224 (15.3%) patients with newly diagnosed tenosynovitis. Compared with non-ADT patients, ADT patients had a lower risk of subsequent tenosynovitis with an adjusted HR of 0.38 [95% confidence interval (CI) 0.28-0.51; P < 0.001]. CONCLUSIONS: ADT use apparently did not increase the risk of tenosynovitis in patients with PCa. Further studies are warranted to assess the clinical significance.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata/tratamento farmacológico , Tenossinovite , Idoso , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Bases de Dados Factuais/estatística & dados numéricos , Monitoramento de Medicamentos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Medição de Risco/métodos , Taiwan/epidemiologia , Tenossinovite/diagnóstico , Tenossinovite/etiologia , Resultado do Tratamento
19.
BMC Cancer ; 19(1): 487, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31122212

RESUMO

BACKGROUND: Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects. METHODS: Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded. DISCUSSION: There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.


Assuntos
Acetato de Abiraterona/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Gosserrelina/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Tioidantoínas/uso terapêutico , Acetato de Abiraterona/administração & dosagem , Antagonistas de Receptores de Andrógenos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Intervalo Livre de Doença , Gosserrelina/administração & dosagem , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Prednisona/administração & dosagem , Qualidade de Vida , Testosterona/sangue , Tioidantoínas/administração & dosagem , Resultado do Tratamento
20.
Breast Cancer Res Treat ; 176(3): 483-494, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31065872

RESUMO

PURPOSE: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. METHODS: We reviewed the current evidence on the drug safety of targeted agents for metastatic breast cancer currently used in clinical practice in Italy, supported by the clinical experience of Italian oncologists with expertise in the field. RESULTS: All oncologists had used CDK4/6 inhibitors in clinical practice and/or within a clinical trial. The clinical management of toxicities, including dose adjustments, treatment interruptions, and concerns regarding special populations is discussed, and the management of relevant adverse events, related to individual agents and class-specific, toxicities is reviewed. Hematologic toxicities have the greatest impact on clinical management of the disease and on patients. Although toxicities associated with the new treatments result in more visits to the physician and more time and attention with patients, they are manageable, with no need for the oncologist to consult with specialist physicians. CONCLUSIONS: Based on the available evidence and current guidelines, we propose a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Feminino , Humanos , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico
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