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1.
Orv Hetil ; 161(20): 813-820, 2020 05 01.
Artigo em Húngaro | MEDLINE | ID: mdl-32364360

RESUMO

In the last few years, several new drugs with various mechanisms of action have been approved for the treatment of castration-resistant prostate cancer. Due to this development, therapeutic decision-making has become increasingly complex. Therefore, therapy selection as well as timing and sequence of treatments need to be optimized in an individual manner. In addition, also for these novel therapies, baseline and acquired as well as cross-resistance have been observed. Underlying mechanisms become increasingly clear, resulting in a shift from empiric-based towards rational-based therapeutic decision-making. In the present review, we provide an overview on the resistance mechanisms against the most frequently applied systemic treatments of metastatic castration-resistant prostate cancer such as docetaxel, abiraterone and enzalutamide. We summarize - among others - the mechanisms by MDR (multidrug-resistant) protein expression, alterations of androgen receptor, Wnt, p53 and DNA-repair pathways (BRCA/ATM) as well as resistance through therapy-induced neuroendocrine differentiation of the tumour. Orv Hetil. 2020; 161(20): 813-820.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androstenos/uso terapêutico , Docetaxel/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Metástase Neoplásica , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Resultado do Tratamento
2.
Anticancer Res ; 40(4): 2303-2309, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234930

RESUMO

BACKGROUND/AIM: To predict pCR during neoadjuvant chemotherapy is still difficult. The aim of this study was to evaluate the optimal tumor reduction rate and modalities for predicting pCR after two cycles of docetaxel. PATIENTS AND METHODS: We analyzed 52 patients with HER2-positive or triple-negative breast cancer. The tumor reduction rate was evaluated after two 3-week cycles of docetaxel (plus trastuzumab for HER2-positive cancer patients). Patients without progression completed two additional cycles of docetaxel and four cycles of an anthracycline-containing regimen. RESULTS: Twenty-eight patients achieved pCR. The optimal tumor reduction rates for predicting pCR were 23, 39, 32, and 40% for US, caliper, MMG, and MRI measurements, respectively. The AUC was highest for caliper measurements. The optimal modality for predicting pCR differed among subtypes. CONCLUSION: Although tumor reduction rate after two cycles of chemotherapy is highly predictive of pCR, the optimal cutoff value differed among the modalities and breast cancer subtype.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Mama/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Antraciclinas/administração & dosagem , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/metabolismo , Docetaxel/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Indução de Remissão , Trastuzumab/administração & dosagem , Carga Tumoral/efeitos dos fármacos , Ultrassonografia
3.
Radiat Oncol ; 15(1): 75, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268925

RESUMO

BACKGROUND: The improvement of survival outcomes and the reduction of toxicities for esophageal squamous cell carcinoma (SCC) are still needed. We conducted a pilot study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin for the treatment of esophageal SCC with T4 and/or M1 lymph node metastasis (LNM) or locoregional recurrence. METHODS: Fifty-four patients with advanced thoracic esophageal SCC having a stage T4 tumor or M1 LNM and/or locoregional recurrence were enrolled. Docetaxel and cisplatin were both administered weekly at a dose of 25 mg/m2 5-6 times in total concurrently with a specific dose of radiation. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), locoregional control and treatment-related toxicities. RESULTS: From October 2015 to December 2016, concurrent treatment with full-cycle docetaxel and cisplatin and radiotherapy was administered to 41 of 54 patients (75.9%). A total of 51 patients (94.4%) completed the radiation schedules. Twenty-one patients (44.4%) achieved a complete response, and 21 (44.4%) achieved a partial response after chemoradiotherapy. The median survival time was 18.2 months, and the median PFS time was 11.5 months. The 1-year and 3-year OS, locoregional control and PFS rates were 70.4, 80.6, 50.0 and 36.4%, 64.3, 31.5%, respectively. Grade 3 toxicities included neutropenia (13.0%), anemia (3.7%), thrombocytopenia (1.9%), fatigue (20.4%), anorexia (13.0%), esophagitis (11.1%), and pneumonitis (5.6%). Grade 4 neutropenia occurred in 16.7% of patients. Four patients (7.4%) died from grade 5 toxicities. There were no significant differences in both survival and grade 3 and higher toxicities between the newly diagnosed group and recurrent group. CONCLUSIONS: Concurrent chemoradiotherapy with weekly docetaxel and cisplatin is a well-tolerated and effective treatment regimen for esophageal SCC with T4 or M1 LNM and/or locoregional recurrence. Clinical trials with larger sample size and comparisons with conventional fluorouracil and cisplatin regimens are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Neoplasias de Células Escamosas/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Neoplasias Esofágicas/patologia , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
4.
Anticancer Res ; 40(4): 2095-2106, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234902

RESUMO

BACKGROUND: The mechanism of action of bevacizumab and erlotinib is quite different in the treatment of advanced non-small cell lung cancer (NSCLC). This study sought to compare the two targeted therapies in terms of sequential tumor response metrics. PATIENTS AND METHODS: Parameters of radiological tumor response evaluation were assessed at baseline and periodically in 58 patients receiving either bevacizumab plus platinum-based chemotherapy (N=25) or erlotinib (N=33). RESULTS: Bevacizumab-treated patients had lower longest diameter at best response compared to the erlotinib group (p=0.011). The longest diameter, tumor volume and density significantly decreased from baseline to best response for the entire cohort and bevacizumab-treated patients; no difference was found in the erlotinib group. CONCLUSION: Treatment with bevacizumab substantially improved tumor metrics between baseline and each cycle of treatment, as well as between baseline and best response, in patients with advanced NSCLC.


Assuntos
Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/administração & dosagem , Cloridrato de Erlotinib/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Docetaxel/efeitos adversos , Cloridrato de Erlotinib/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento
5.
Asian Pac J Cancer Prev ; 21(3): 749-754, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212803

RESUMO

BACKGROUND: Triple-negative breast(TNBC) cancer is a molecular subtype of breast cancer with poor prognosis and did not get approved targeted therapy till now. In the last years, metronomic chemotherapy (mCTH) was investigated to improve treatment outcomes in TNBC patients both in early and metastatic setting due to its anti-angiogenic and immune-stimulatory mechanisms. The aim of this study is to evaluate the efficacy and safety of extended adjuvant chemotherapy with metronomic docetaxel for patients with operable TNBC. METHODS: 31 women with clinically and pathologically proved operable TNBC, either node-negative or node-positive with tumor size ≥ 0,5 cm were enrolled after finishing the primary standard of care treatment.  The patients were subjected to extended adjuvant therapy for 6 months with metronomic low dose docetaxel with starting dose of 15mg/m2 in weekly bases for 4 weeks then the dose was escalated to 20 mg/m2 once per week if there were no side effects. RESULTS: After a median follow up of 36 months (range 6-52), 24 patients (77.4%) were still alive. During the period of follow-up, 12 patients (38.7%) showed disease relapse and 19(61.3%) cases remain free of the disease. The estimated mean of DFS in our study was 38.26 months (95%CI; 31.87 - 44.65) with 2 and 3 years DFS rate of 70.5 % and 56.4% respectively while  the estimated mean of OS was 43.75 months (95% CI; 38.35 - 49.16) with 2 and 3 years OS rates 83.3% and 78.1% respectively, Generally the treatment was tolerated with mild to moderate hematological and non hematological adverse events, all are grade 1,2 and treatment-related deaths were not observed. CONCLUSION: Extended adjuvant treatment for 6 months with metronomic docetaxel after the primary standard of care therapy was tolerated and has an encouraging survival benefit in patients with operable TNBC and these results need further evaluation in randomized control studies.
.


Assuntos
Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/diagnóstico
6.
Asian Pac J Cancer Prev ; 21(3): 825-830, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212813

RESUMO

OBJECTIVE: To evaluate the response rate of Cisplatin plus Docetaxel in the treatment of locally advanced head and neck squamous cell carcinomas (HNSCC) at a tertiary care hospital in Karachi, Pakistan. MATERIALS AND METHODS: It was a longitudinal study, conducted at the Department of Medical Oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan from December 2018 to June 2019. One hundred patients of age 14-66 years of age of either gender with histologically proven Squamous Cell Carcinoma of Head and Neck, Stage III and IV (locally advanced) with no distant metastases were included in the study. Patients who were declared unresectable by the otolaryngologist and those with delayed appointment for radiation were given 3 cycles of Induction Chemotherapy with Cisplatin and Docetaxel, both at a dose of 75mg/m2 3 weekly. After 3 cycles, CT scan was repeated to assess the clinical response. Those patients who had partial or complete response as per RECIST criteria were re-assessed by the otolaryngologist and were planned for surgery if disease became resectable while other patients were referred for Concurrent Chemo-Radiation Therapy (CCRT). SPSS version 23 was used to analyze data. RESULTS: The partial response was achieved in majority of the patients after Induction Chemotherapy with Docetaxel and Cisplatin (62%) with a complete response in 12 %. However, 22% showed progression of the disease, and 4% showed stable disease. The most frequent side effects observed were diarrhea (62%) and neutropenia (57%). CONCLUSION: Induction chemotherapy with Cisplatin and Docetaxel is a promising regimen with good response and favorable toxicity profile and can be considered as a potentially effective outpatient regimen for locally advanced squamous cell carcinoma of head and neck.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Cisplatino/administração & dosagem , Progressão da Doença , Docetaxel/administração & dosagem , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Zhonghua Zhong Liu Za Zhi ; 42(2): 133-138, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32135648

RESUMO

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions: Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn't affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Terapia Combinada , Docetaxel/administração & dosagem , Cronoterapia Farmacológica , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento
8.
Cancer Immunol Immunother ; 69(5): 847-857, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32025848

RESUMO

A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with ≥ 26% lymphocytes or PSA levels of < 11.2 ng/ml, but further clinical trials comparing OS are required.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/terapia , Linfócitos T Citotóxicos/imunologia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/imunologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Critérios de Avaliação de Resposta em Tumores Sólidos , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/efeitos adversos , Vacinas de Subunidades/imunologia
9.
Medicine (Baltimore) ; 99(5): e18646, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000369

RESUMO

INTRODUCTION: Clear cell adenocarcinoma of the cervix (CCAC), a rare and more severe type of gynecological cancer, is especially rare in pediatric patients. Traditionally, surgery following chemotherapy (CT) and radiation therapy is the preferred treatment for CCAC; however, patients have poor 5-year survival rates than other types of cervical cancers. PATIENT CONCERNS: A 6-year-old girl with a history of vaginal discharge for 18 months was diagnosed with CCAC by histological examination. Her parents refused the traditional treatment of radical hysterectomy and lymph node dissection because of her young age. DIAGNOSIS: The patient's tests revealed negative human papilloma virus and negative methylated paired box 1 gene results. The tumor mass histopathology revealed stage IIA1 CCAC that originated from the cervix. INTERVENTIONS: Tumor mass excision with preservation of the cervix by electrosurgical biopsy under hysteroscopy was performed. Four cycles of docetaxel and oxaliplatin CT were administered every 3 weeks. OUTCOMES: No signs of recurrence were observed in the 28 months after final treatment and diagnosis on magnetic resonance imaging, color ultrasonic imaging, and gynecological examination. Serologic tumor biomarkers were also within normal ranges. CONCLUSIONS: This is the first reported CCAC case in which the primary treatment included electrosurgical biopsy of the polypoid mass under hysteroscopy, followed by CT without traditional treatment: radical surgery with pelvic and/or lymphadenectomy for fertility preservation. This is a new treatment approach for young CCAC patients without the use of surgery.


Assuntos
Adenocarcinoma/cirurgia , Histeroscopia , Tratamentos com Preservação do Órgão , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Antineoplásicos/uso terapêutico , Colo do Útero/patologia , Criança , Docetaxel/uso terapêutico , Feminino , Humanos , Oxaliplatina/uso terapêutico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia
10.
Bull Cancer ; 107(1): 54-60, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31980145

RESUMO

FLOT-4 study recently reports that in patients with gastric cancer, perioperative chemotherapy with 5-fluorouracile, leucovorin, oxaliplatin and docetaxel (FLOT regimen) increases survival over standard ECF/ECX regimen (epirubicine, cisplatine and 5-fluorouracile [or capecitabine]). Does this study, make FLOT a new standard of perioperative chemotherapy for localized gastric cancer? Seven hundred and sixteen patients were included into that randomized study. Thirty seven per cent and 46% of the patients received the full planned treatment in the ECF/ECX group and in the FLOT group, respectively. The primary aim of FLOT-4 was met as FLOT significantly reduced the relative risk of death vs. ECF/ECX (HR: 0.77; 95% CI: 0.63-0.94; P=0.012). Median survival is increased by 15 months with FLOT (50 months vs. 35 months). FLOT also provided better complete resection rates, better complete pathological response rates, and better disease-free survival than ECF/ECX. FLOT is more likely associated with the following adverse events: diarrheas, leuco-neutropenia (including 51% of severe ones), infections (including 18% of severe ones), and peripheral neuropathy. On the contrary, ECF/ECX provided more likely severe nausea and vomiting, severe anemia, and thromboembolic events. Overall, the number of patients with related serious adverse events (including those that occurred during hospital stay for surgery) was similar in the two groups, as was the number of toxic deaths and postoperative deaths. FLOT should be regarded as the recommended perioperative chemotherapy for patients with gastric cancer or adenocarcinoma of the gastro-esophageal junction. However, some doubts remain as regards of its use in the daily practice for unselected patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Epirubicina/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Oxaliplatina/administração & dosagem , Assistência Perioperatória/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
11.
Anticancer Res ; 40(1): 109-119, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892559

RESUMO

BACKGROUND/AIM: Although molecular targeting therapy is an attractive treatment for cancer, resistance eventually develops in most cases. Here, we evaluated chemotherapeutic efficacy on non-small cell lung cancer (NSCLC) with acquired resistance to epidermal growth factor receptor inhibitors mechanistically. MATERIALS AND METHODS: Antitumor effects of taxotere were evaluated using multiple models, including xenograft, and patient-derived models developed from adenocarcinoma cancer patients. Protein expressions were analyzed after drug treatment. RESULTS: Taxotere inhibited tumor growth of NSCLC cells harboring drug resistance, and reduced the expression of phosphorylated MET proto-oncogene, receptor tyrosine kinase (MET). A tumor-inhibitory effect of taxotere was also demonstrated in vivo in xenografts in mice, patient-derived primary lung tumor cells and patient-derived xenograft with concomitant repression of phosphorylated MET expression. Chemotherapeutic and MET-targeting drug exhibited a synergistic cell growth-inhibitory effect. CONCLUSION: These results suggest that the anticancer drug taxane may be an adjuvant for lung tumors exhibiting enhanced signaling of MET networks.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Anticancer Res ; 40(1): 335-339, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892584

RESUMO

BACKGROUND/AIM: The novel taxane cabazitaxel has been shown to exert excellent anticancer effects after androgen receptor axis-targeting (ARAT) agents in clinical data, but not in in vitro data. We investigated the clinical outcome of cabazitaxel chemotherapy after docetaxel according to use of ARAT agents. PATIENTS AND METHODS: Prostate specific antigen (PSA) response, progression-free survival, and overall survival were compared between cases with and without prior use of ARAT agents in 74 Japanese patients with metastatic castration-resistant prostate cancer treated with cabazitaxel chemotherapy. RESULTS: Background characteristics were comparable between patients with and without prior use of ARAT agents. PSA response, progression-free survival, and overall survival in cabazitaxel chemotherapy were comparable between patients with and without prior use of ARAT agents. CONCLUSION: No detrimental effects of prior ARAT agents on clinical outcome were observed for cabazitaxel chemotherapy in the post-docetaxel setting, suggesting that cabazitaxel can be expected to remain active even after ARAT agent therapy.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Docetaxel/farmacologia , Terapia de Alvo Molecular , Receptores Androgênicos/metabolismo , Taxoides/farmacologia , Idoso , Antagonistas de Receptores de Andrógenos/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Masculino , Prognóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Resultado do Tratamento
15.
J Biomed Nanotechnol ; 16(1): 40-53, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996284

RESUMO

In recent decades, a large number of research studies have been conducted to improve the treatment strategy against epithelial ovarian cancer, but women in advanced stage still have poor outcomes. The development of advanced treatments must be continued to overcome the limitation. Docetaxel, a semi-synthetic product derived from the Pacific Taxus extract, has been studied for many years for its potent anticancer applications. Aiming to solve the problems of its highly lipophilicity, insolubility and adverse side effects, nanocarriers were applied. Relying on the integration of nanoparticles which had optimized sizes, shapes, and surface properties, the effect of docetaxel was enhanced. In this study, we designed a novel drug loaded gel-forming nanoparticle system (Doc-NMs-hydrogel composites), which acted as a sustained drug depot for docetaxel. Docetaxel was encapsulated into MPEG-PCL and then into blank thermosensitive hydrogel Pluronic F-127. Characterization showed that the prepared Doc-NMs had high drug loading (7%), minor particle size (37 nm), relatively good water solubility. Moreover, the cytotoxicity, apoptosis induction and the antitumor effects of Doc-NMs-hydrogel composites on mice abdominal SKOV-3 ovarian cancer model were investigated in vivo. Compared with other groups, at the same dosage, Doc-NMs-hydrogel composites show better apoptosis induction and cell growth inhibition. In conclusion, the prepared Doc-NMs-hydrogel composites enhanced anti-tumor activity by increasing local docetaxel concentration, maintaining stable and sustained drug release, prolonging drug retention time in tumors, and reducing toxicity to normal tissues. Doc-NMs-hydrogel composites might have great potential clinical application in anti-ovarian cancer activity.


Assuntos
Neoplasias Ovarianas , Animais , Antineoplásicos , Linhagem Celular Tumoral , Docetaxel , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Hidrogéis , Camundongos , Micelas , Nanopartículas , Taxoides
16.
Cancer Sci ; 111(4): 1103-1112, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31981293

RESUMO

The association between the tumor microenvironment (TME) and treatment response or survival has been a recent focus in several types of cancer. However, most study materials are resected specimens that were completely modified by prior chemotherapy; therefore, the unmodified host immune condition has not yet been clarified. The aim of the present study was to evaluate the relationship between TME assessed in pre-therapeutic biopsy samples and chemoresistance in esophageal cancer (EC). A total of 86 endoscopic biopsy samples from EC patients who received neoadjuvant chemotherapy (NAC) prior to surgery were evaluated for the number of intratumoral CD4+ lymphocytes (with/without Foxp3 expression), CD8+ lymphocytes (with/without PD-1 expression), monocytes (CD14+ ) and macrophages (CD86+ , CD163+ and CD206+ ) by multiplex immunohistochemistry (IHC). The number of tumor-infiltrating CD206+ macrophages I significantly correlated with cT, cM, cStage and neutrophil/lymphocyte ratio (NLR), whereas the number of lymphocytes (including expression of Foxp3 and PD-1) was not associated with clinico-pathological features. The high infiltration of CD163+ or CD206+ macrophages was significantly associated with poor pathological response to NAC (P = 0.0057 and 0.0196, respectively). Expression of arginase-1 in CD163+ macrophages tended to be higher in non-responders (29.4% vs 18.2%, P = 0.17). In addition, patients with high infiltration of M2 macrophages exhibited unfavorable overall survival compared to those without high infiltration of M2 macrophages (5-year overall survival 57.2% vs 71.0%, P = 0.0498). Thus, a comprehensive analysis of TME using multiplex IHC revealed that M2 macrophage infiltration would be useful in predicting the response to NAC and long-term survival in EC patients.


Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Terapia Neoadjuvante , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Biomarcadores Tumorais/sangue , Biópsia , Linhagem da Célula/efeitos dos fármacos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fatores de Transcrição Forkhead/sangue , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/sangue , Receptor de Morte Celular Programada 1/genética , Receptores de Superfície Celular/sangue , Microambiente Tumoral/efeitos dos fármacos
17.
Cancer Sci ; 111(4): 1303-1313, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31994271

RESUMO

The survival benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy in oral squamous cell carcinoma (OSCC) patients is not satisfactory. Previously, we identified that stathmin, a microtubule-destabilizing protein, is overexpressed in OSCC. Here, we further investigated its role as a biomarker that impacts on OSCC chemosensitivity. We analyzed the predictive value of stathmin on TPF induction chemotherapy and its impact on OSCC cell chemosensitivity. Then, we further investigated the therapeutic effects of the combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors in vitro and in vivo. We found that OSCC patients with low stathmin expression benefited from TPF induction chemotherapy, while OSCC patients with high stathmin expression could not benefit from TPF induction chemotherapy. Stathmin overexpression promoted cellular proliferation and decreased OSCC cell sensitivity to TPF treatment. In addition, inhibition of the PI3K-AKT-mTOR signaling pathway decreased stathmin expression and phosphorylation. The combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors exhibited a potent antitumor effect both in vitro and in vivo. Therefore, stathmin can be used as a predictive biomarker for TPF induction chemotherapy and a combination therapy regimen based on stathmin expression might improve the survival of OSCC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Estatmina/genética , Idoso , Animais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Medicina de Precisão , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Taxoides/administração & dosagem
18.
Pharm Res ; 37(3): 36, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965346

RESUMO

PURPOSE: We describe the preparation of injectable polymeric paste (IPP) formulations for local and sustained release of drugs. Furthermore, we include the characterization and possible applications of such pastes. Particular attention is paid to characteristics relevant to the successful clinical formulation development, such as viscosity, injectability, degradation, drug release, sterilization, stability performance and pharmacokinetics. METHODS: Paste injectability was characterized using measured viscosity and the Hagen-Poiseuille equation to determine injection forces. Drug degradation, release and formulation stability experiments were performed in vitro and drug levels were quantified using HPLC-UV methods. Pharmacokinetic evaluation of sustained-release lidocaine IPPs used five groups of six rats receiving increasing doses subcutaneously. An anti-cancer formulation was evaluated in a subcutaneous tumor xenograft mouse model. RESULTS: The viscosity and injectability of IPPs could be controlled by changing the polymeric composition. IPPs demonstrated good long-term stability and tunable drug-release with low systemic exposure in vivo in rats. Preliminary data in a subcutaneous tumor model points to a sustained anticancer effect. CONCLUSIONS: These IPPs are tunable platforms for local and sustained delivery of drugs and have potential for further clinical development to treat a number of diseases.


Assuntos
Portadores de Fármacos/química , Composição de Medicamentos/métodos , Pomadas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Anilidas/química , Anilidas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Docetaxel/química , Docetaxel/farmacologia , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Injeções , Lidocaína/química , Lidocaína/farmacocinética , Masculino , Camundongos , Camundongos Nus , Neoplasias Experimentais , Nitrilos/química , Nitrilos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Ratos , Compostos de Tosil/química , Compostos de Tosil/farmacologia , Viscosidade
19.
Chem Biodivers ; 17(2): e1900631, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31967396

RESUMO

A mixture of taxols was prepared from 10-deacetyl-7-xylosyltaxanes by three-step reactions: redox, acetylation, and deacetylation. The mixture was separated by column chromatography on silica gel to afford Taxol, Taxol B (Cephalomannine) and Taxol C. The mixture of Taxol B and Taxol C was converted to Docetaxel by Schwartz's reagent. The structures of Taxol and Docetaxel were characterized by HPLC, 1 H-NMR, 13 C-NMR and MS. This synthetic process has expanded the source of biomass for the chemical semi-synthesis of Taxol and Docetaxel, reduced the production costs, and increased the biomass resource of taxanes.


Assuntos
Docetaxel/química , Paclitaxel/química , Taxoides/química , Acetilação , Cromatografia Líquida de Alta Pressão , Docetaxel/síntese química , Espectroscopia de Ressonância Magnética , Oxirredução , Paclitaxel/síntese química
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