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1.
Medicine (Baltimore) ; 99(2): e18591, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914038

RESUMO

This analysis aimed to investigate whether the long-term administration of temozolomide (TMZ) claimed a survival advantage for patients with glioblastoma in China.A total of 75 patients with newly diagnosed glioblastoma at the Department of Radiation Oncology, Shenzhen People's Hospital between August 2008 and August 2016 were retrospectively evaluated during analysis. A propensity-matched analysis was performed to balance the basic characteristics of patients between compared groups. Kaplan-Meier method and Cox proportional hazards model were used to assess progression-free survival (PFS) and overall survival (OS) of patients receiving 6 adjuvant TMZ cycles compared with patients treated with more than 6 cycles.Twenty of 75 patients received more than 6 cycles of TMZ, and the other 55 patients were treated with a median of 6 cycles ranging from 1 to 6. The patients with long-term administration of TMZ had better OS (47.0 months, 95% CI 20.0-73.9 vs 20.6 months, 95% CI 17.9-23.2, P = .014) but not PFS (17.0 months, 95% CI 10.1-24.5 vs 14.2 months, 95% CI 11.8-16.6, P = .133). Balancing the clinical factors with a propensity-matched analysis also showed the significant advantage of prolonged TMZ application in terms of OS but not PFS.Prolonged administration of TMZ beyond 6 cycles did demonstrate survival benefits for patients with initially diagnosed glioblastoma.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Temozolomida/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/terapia , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Glioblastoma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Pontuação de Propensão , Estudos Retrospectivos , Temozolomida/administração & dosagem , Adulto Jovem
3.
BMC Cancer ; 19(1): 961, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619207

RESUMO

BACKGROUND: Neuroblastoma is the most common extra-cranial solid tumor among children. Despite intensive treatment, patients with advanced disease mostly experience dismal outcomes. Here, we proposed the use of topotecan and cyclophosphamide containing induction regimen as an upfront therapy to high risk neuroblastoma patients. METHODS: Patients with high risk neuroblastoma undergoing ThaiPOG high risk neuroblastoma protocol from 2016 to 2017 were studied. All patients received 6 cycles of induction regimen consisting of 2 cycles topotecan (1.2 mg/m2/day) and cyclophosphamide (400 mg/m2/day) for 5 days followed by cisplatin (50 mg/m2/day) for 4 days combined with etoposide (200 mg/m2/day) for 3 days on the third and fifth cycles and cyclophosphamide (2100 mg/m2/day) for 2 days combined with doxorubicin (25 mg/m2/day) and vincristine (0.67 mg/m2/day) for 3 days on the fourth and sixth cycles. Treatment response after the 5th cycle before surgery and treatment-related toxicities after each topotecan containing induction cycle were evaluated. Relevant prognostic factors were analyzed to measure the treatment response among those patients. RESULTS: In all, 107 high risk neuroblastoma patients were enrolled in the study. After the 5th cycle of induction regimen, the patients achieved complete response (N = 2), very good partial response (N = 40), partial response (N = 46) and mixed response (N = 19). None of the patients experienced stable disease or disease progression. The most significant prognostic factor was type of healthcare system. The most common adverse effect was febrile neutropenia followed by mucositis, diarrhea and elevated renal function. CONCLUSION: The topotecan and cyclophosphamide containing induction regimen effectively provides favorable treatment response. The regimen is well tolerated with minimal toxicity among patients with high risk neuroblastoma in Thailand.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Quimioterapia de Indução/métodos , Neuroblastoma/tratamento farmacológico , Inibidores da Topoisomerase I/uso terapêutico , Topotecan/uso terapêutico , Adolescente , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos Prospectivos , Tailândia , Inibidores da Topoisomerase I/administração & dosagem , Topotecan/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/uso terapêutico
4.
In Vivo ; 33(5): 1609-1614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471412

RESUMO

BACKGROUND/AIM: Trabectedin is a synthetic antineoplastic agent approved for advanced soft tissue sarcoma (STS) in Japan. The aim of this study was to evaluate the efficacy and safety of the Japan-approved dose of trabectedin for advanced STS. PATIENTS AND METHODS: We retrospectively reviewed 38 patients with advanced STS who received salvage chemotherapy with trabectedin. RESULTS: The overall response and disease control rates were 16% (5 patients) and 67% (20 patients), respectively. The median progression-free and overall survival were 7.3 and 17.8 months, respectively. There were no significant differences between patients with liposarcoma or leiomyosarcoma and those without, or between patients with TRS and those without. The most common grade 3-4 AEs were elevated transaminases and neutropenia. CONCLUSION: Trabectedin 1.2 mg/m2, as the approved dose in Japan, showed similar efficacy to the dose of 1.5 mg/m2 used in Western countries. Trabectedin could be an option for advanced STS in Japan, regardless of histological subtype.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Sarcoma/tratamento farmacológico , Trabectedina/uso terapêutico , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Biomarcadores Tumorais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Sarcoma/diagnóstico , Sarcoma/etiologia , Sarcoma/mortalidade , Trabectedina/administração & dosagem , Trabectedina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
5.
J Clin Neurosci ; 68: 39-44, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31399318

RESUMO

The standard medical care of glioblastoma (GBM) patients with good performance status is based on focal brain radiotherapy (40-60 Gy) with concurrent temozolomide (TMZ) followed by adjuvant TMZ. Newly diagnosed multifocal and/or multicentric GBM (M/M GBM) cases are usually treated with TMZ alone: whole brain chemoradiotherapy (CRT) is avoided for safety reasons. To our knowledge, no study has investigated the safety and efficacy of whole-brain radiotherapy (WBRT) with concurrent TMZ in M/M GBM patients. This retrospective study sought to assess the role of WBRT associated with concurrent TMZ followed by TMZ alone in this population. Eleven patients with pathologically proven M/M GBM (≥3 lobes) were treated with WBRT between April 2009 and September 2017. The median age was 50 years [34-74]. The median dose of radiotherapy was 45 Gy at 1.8 Gy per fraction over 37 days [29-41], with concurrent daily TMZ at the dose of 75 mg/m2. This treatment was followed by adjuvant monthly TMZ (150 mg/m2-D1-D5). All pathology slides and radiology images were reviewed. The median overall and progression-free survival times for all patients were 10 months [4-25] and 5 months [3-21], respectively. There was no grade 3-4 toxicity due to radiotherapy. One patient stopped the TMZ during the radiochemotherapy period and 9 patients received adjuvant TMZ with a median number of 5 cycles [2-8]. Our study supports the safety and the efficacy of WBRT with TMZ in newly diagnosed M/M GBM. Larger prospective studies are needed to support our results.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Irradiação Craniana/métodos , Glioblastoma/terapia , Temozolomida/administração & dosagem , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/patologia , Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Temozolomida/efeitos adversos
6.
Med Oncol ; 36(9): 80, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399784

RESUMO

The aim of our study is to investigate the efficacy of metronomic cyclophosphamide plus low dose of corticosteroids in advanced or metastatic castration-resistant prostate cancer (CRPC) before, between, and after standard chemotherapy, such as docetaxel and cabazitaxel, and new hormonal treatments, such as abiraterone and enzalutamide. A retrospective analysis was performed on 37 patients. Cyclophosphamide was given orally 50 mg per day together with low dose of corticosteroids, namely dexametasone orally 1 mg per day or prednisone 10 mg per day. Seventeen patients (51%) showed a PSA decline≥ 50%. Median progression-free survival (PFS) and overall survival (OS) were 11 and 28 months, respectively. Median PFS and OS in the subgroup of patients with a PSA decline ≥ 50% were 14 and 35 months, respectively. Treatment was very well tolerated. We suggest that oral metronomic cyclophosphamide plus low dose of oral dexamethasone or prednisone may be a good and safe therapeutic option not only in those CRPC patients unfit for standard treatments but also in those heavily pre-treated patients.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Ciclofosfamida/administração & dosagem , Glucocorticoides/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento
7.
Int J Hyperthermia ; 36(1): 794-800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31450986

RESUMO

Background: Isolated limb perfusion (ILP) is a treatment option for malignancies localized to an extremity and is performed by surgical isolation of the limb which is connected to an extracorporeal circulation system. A high concentration of a chemotherapeutic agent is perfused through the limb, while systemic toxicity is avoided. Currently, the use of packed red blood cells in the priming solution is the norm during ILP. The aim of this study was to investigate the possibility to replace an erythrocyte-based prime solution with a crystalloid-based prime solution while maintaining the regional metabolic oxygen demand during ILP. Methods: In a single-center, randomized controlled, non-blinded, non-inferiority clinical trial, 21 patients scheduled for treatment with ILP were included and randomized 1:1 to either an erythrocyte-based prime solution (control) or a crystalloid-based prime solution (intervention). Results: There was a significant difference in lactate level (mmol/L) during the perfusion between the intervention group and the control group (1.6 ± 0.4 vs. 3.6 ± 0.7, p = .001). No significant differences in oxygen extraction (%) (22 ± 11 vs. 14 ± 4, p = .06), oxygen delivery (ml/min) (90 ± 49 vs. 108 ± 38, p = .39), oxygen consumption (ml/min) (14 ± 2 vs. 14 ± 5, p = .85), regional central venous saturation (%) (83 ± 10 vs. 91 ± 4, p = .07) or INVOS (%) (76 ± 14 vs. 81 ± 11, p = .42) were found between the intervention group and the control group. Conclusion: This study showed no significant improvement with the addition of packed red blood cells into the prime solution in ensuring the metabolic oxygen demand in the treated extremity during ILP, and we, therefore, recommend that a crystalloid-based prime solution should be used.


Assuntos
Soluções Cristaloides/administração & dosagem , Eritrócitos , Extremidades , Perfusão , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Melanoma/terapia , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Sarcoma/terapia , Neoplasias Cutâneas/terapia , Adulto Jovem
8.
Ann Pharm Fr ; 77(5): 426-434, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31288930

RESUMO

OBJECTIVES: The oral route is becoming increasingly important in the panel of anti-cancer therapeutics, but it generates difficulties (adherence, management of adverse effects...). In order to secure medication management, the pharmaceutic team chose to set up pharmaceutical consultations. Its objectives are multiple: understanding of treatment for better adherence, pharmaceutical analysis, enhancement of the city-hospital link. This work presents the setting up of the pharmaceutical consultations and makes an assessment after one year. METHODS: The initial step was a meeting with institutional health professionals who work with patients to define the place, the objectives, and the patients targeted by the pharmaceutical consultation. The targeted patients are all patients receiving temozolomide and some patients initiating oral chemotherapy, considered at risk, on medical solicitation. Documents were created to standardize practices in the team from the collection of information and pharmaceutical analysis until the conduct of the consultation and the consultation report (integrated into the computerized patient's medical file). Activity indicators were defined and collected. RESULTS: Over one year, 65 pharmaceutical consultations were conducted, of which 23 % resulted in pharmaceutical interventions. The average duration of consultation was 34minutes. The whole team (four pharmacists and two residents) was involved in this activity. CONCLUSIONS: Pharmaceutical consultations help secure medical care of patients, providing tools, dedicated and personalized time, pharmaceutical analysis, etc. Ultimately, the goal is to accompany the patient throughout his treatment by having follow-up pharmaceutical consultations, in collaboration with community pharmacists thanks to the city-hospital link that we have established.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Encaminhamento e Consulta , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Prestação Integrada de Cuidados de Saúde , Feminino , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Farmacêuticos , Temozolomida/administração & dosagem , Temozolomida/uso terapêutico
9.
AAPS PharmSciTech ; 20(7): 259, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332574

RESUMO

The local delivery of chemotherapy drugs using implantable drug delivery systems is a promising strategy to the treatment of malignant brain tumors. In this study, core/shell chitosan-poly ethylene oxide-carbon quantum dots/carboxymethyl cellulose-polyvinyl alcohol (CS-PEO-CQDs/CMC-PVA) nanofibers were successfully prepared through coaxial electrospinning as a biodegradable polymeric implant for the local delivery of temozolomide (TMZ). Fluorescent carbon dots with carboxyl-rich surface were used as a trackable drug delivery agent for the localized cancer treatment. The effects of several preparation parameters such as voltage, shell to core flow rate, CS/PEO ratio, and PVA/CMC ratio on the structure of nanofibers were investigated. The best nanofibers were obtained in the condition of CS/PEO ratio of 80:20, CMC/PVA ratio of 20:80, shell to core flow rate of 3, and voltage of 25 V. SEM images showed that such nanofibers possess a smooth surface and bead-less structures. The results obtained by DSC indicated that TMZ trapped in the nanofibers existed in an amorphous or disordered crystalline status. In vitro release profile of TMZ from core-shell nanofibers had biphasic patterns. After an initial burst, a continuous drug release was observed for up to 28 days. The in vitro antitumor activity of CQDs-TMZ was tested against the tumor U251 cell lines than the free drug. It has been found that the cytotoxicity of TMZ to U251 cancer cells is enhanced when TMZ is conjugated with CQDs.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Nanofibras/química , Pontos Quânticos/química , Temozolomida/administração & dosagem , Antineoplásicos Alquilantes/química , Carboximetilcelulose Sódica/química , Linhagem Celular Tumoral , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Humanos , Polietilenoglicóis/química , Álcool de Polivinil/química , Temozolomida/química
10.
J Med Food ; 22(9): 896-906, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31216204

RESUMO

The present study investigated the immunomodulatory activity and associated mechanisms of heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) in a cyclophosphamide (CTX)-induced mouse model of immunosuppression. HT-LM1004 induced phagocytic activity and nitric oxide production in RAW264.7 macrophages and stimulated the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, and IL-12p70. In mice with CTX-induced immunosuppression, oral HT-LM1004 administration restored thymus and spleen indices, including spleen weight. Consistent with the in vitro results, HT-LM1004 increased TNF-α, IFN-γ, IL-2, and IL-12p70 levels in mice after 14 days of treatment and enhanced the natural killer (NK) cell activity of splenocytes from mice with CTX-induced immunosuppression against YAC-1 lymphoma cells. The method of HT-LM1004 generation influenced this activity: L. plantarum LM1004 grown in a membrane bioreactor, which reduced the size of the cells to <1.0 µm through physical stress (micronization), promoted NK cell cytotoxicity to a greater extent than LM1004 subjected to heat treatment alone. These findings indicate that HT-LM1004 without or with micronization can reverse CTX-induced immunosuppression without adverse side effects by potentiating NK cell function.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Ciclofosfamida/efeitos adversos , Fatores Imunológicos/administração & dosagem , Imunomodulação/efeitos dos fármacos , Lactobacillus plantarum/química , Probióticos/administração & dosagem , Animais , Antineoplásicos Alquilantes/administração & dosagem , Ciclofosfamida/administração & dosagem , Feminino , Temperatura Alta , Imunossupressão , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
11.
Cancer Imaging ; 19(1): 31, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146793

RESUMO

OBJECTIVE: To investigate the outcome and safety data of chemosaturation with percutaneous hepatic perfusion (CS-PHP) of melphalan in patients with liver-dominant metastatic uveal melanoma. MATERIAL AND METHODS: This is a HIPAA compliant, IRB approved, retrospective study. A total of 28 CS-PHPs were performed in 16 individual patients (six men and ten women, median age 63.1 years [range 49.1 to 78.7 years], one to six CS-PHP procedures per patient) for treatment of liver-dominant metastatic uveal melanoma between June, 2015 and December, 2018. All patients received cross-sectional imaging at baseline and during follow-up. CS-PHP was performed with the Hepatic CHEMOSAT® Delivery System (Delcath Systems, Inc., NY, USA) facilitating extracorporeal filtration of hepatic blood for melphalan removal. Ideal body weight-adjusted melphalan doses were administered into the hepatic arteries. Serious adverse events (SAE), progression-free survival based on response criteria in solid tumors, and overall survival were noted. Survival data were analyzed using Kaplan-Meier estimates. RESULTS: Partial response after first CS-PHP was observed in nine patients (60%), stable disease in five patients (33%) and progressive disease in one patient (7%). Median overall survival was 27.4 months (95% CI 4.1 to 35.4 month) after first CS-PHP. Median progression-free survival was 11.1 months after first CS-PHP (95% CI 4.9 to 23.6 months). SAEs were observed in the majority of patients with most SAEs limited to grades one and two. Thirteen SAEs of grades three and four were observed in seven individual patients. No grade five SAE was observed. CONCLUSION: CS-PHP is an efficacious and safe treatment for patients presenting with liver-dominant metastatic uveal melanoma.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional/métodos , Melanoma/terapia , Melfalan/administração & dosagem , Neoplasias Uveais/terapia , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/instrumentação , Feminino , Humanos , Circulação Hepática , Masculino , Melanoma/patologia , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Uveais/patologia
12.
BMJ Case Rep ; 12(5)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31154345

RESUMO

Glioblastoma multiforme (GBM) is an aggressive tumour that can lead to lymphopaenia. Its standard treatment involves temozolomide (TMZ) chemotherapy with radiation, often with addition of corticosteroids for symptomatic management. Although TMZ is also immunosuppressive, patients receiving TMZ rarely develop disseminated opportunistic infections. Here, we report the case of a patient with GBM receiving TMZ, radiotherapy and corticosteroids, who develops an incidental new brain lesion that is found to be disseminated Aspergillus within a new GBM tumour site. The patient received successful early treatment of her central nervous system aspergillosis. This case illustrates the profound immunosuppressive potential of GBM in conjunction with TMZ and corticosteroids, which can lead to high-morbidity opportunistic infections concurrently with tumour progression. Future research is needed to elucidate GBM, TMZ and corticosteroids' compound immune effects and guide management that strikes a balance between treating high-morbidity infections and continuing with immunosuppressive chemotherapy.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Aspergilose/diagnóstico , Abscesso Encefálico/diagnóstico , Neoplasias Encefálicas/terapia , Lobo Frontal , Glioblastoma/terapia , Temozolomida/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Aspergilose/diagnóstico por imagem , Aspergilose/etiologia , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/etiologia , Neoplasias Encefálicas/patologia , Terapia Combinada , Diagnóstico Diferencial , Feminino , Glioblastoma/patologia , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Temozolomida/administração & dosagem , Temozolomida/efeitos adversos
13.
Cardiovasc Intervent Radiol ; 42(10): 1441-1448, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31089781

RESUMO

PURPOSE: To evaluate the feasibility of 2D-perfusion angiography (2D-PA) for detecting leakage of the double-balloon catheter used for chemosaturation percutaneous hepatic perfusion (CS-PHP). MATERIALS AND METHODS: Overall, 112 CS-PHP (09/2015-09/2018) in 52 patients were retrospectively screened for leakage alongside the double-balloon catheter on standard venograms. Finally, 18 procedures with visually detected leakage were included. Fifteen consecutive procedures without leakage served as control. To evaluate 2D-PA for leakage detection, the acquired digital subtraction venograms were post-processed. For each balloon, two different target ROIs were evaluated to assess a possible impact of localization and shape of the ROIs. Time to peak (TTP), peak density (PD), area under the curve (AUC), and ratios of target ROI/reference ROIs (PDtROI/PDREF; AUCtROI/AUCREF; and TTPtROI/TTPREF) were calculated. RESULTS: Leakages were located as follows: 15/18 cranial and 3/18 caudal. At the cranial balloon both ROIs showed a significant decrease in PDtROI/PDREF and AUCtROI/AUCREF (ROI1: p < 0.0001; p < 0.0001; ROI2: p < 0.0001; p < 0.0001) and a significant increase in TTPtROI/TTPREF (ROI1: p = 0.0009; ROI2: p = 0.0003) after double-balloon correction. Following balloon adjustment, the 2D-PA ratios (PD and AUC) of the tested ROIs differed significantly (p < 0.05). The inter-individual comparison of the 2D-PA parameters of the group with leakage before balloon correction and the non-leakage group showed significantly different 2D-PA values for the cranial balloon in both ROIs (p < 0.05). No significant differences were found for the caudal balloon. CONCLUSION: 2D-PA provides a feasible tool for detecting leakages alongside the cranial portion of the double-balloon catheter used in CS-PHP. The shape and position of the ROIs used to assess perfusion and flow have an impact on the measurements.


Assuntos
Angiografia Digital/métodos , Antineoplásicos Alquilantes/uso terapêutico , Cateterismo/instrumentação , Quimioterapia do Câncer por Perfusão Regional/métodos , Neoplasias Hepáticas/tratamento farmacológico , Melfalan/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Cateterismo/métodos , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
14.
Vet Clin Pathol ; 48(2): 255-258, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31062418

RESUMO

A 9-year-old mixed breed 13 kg spayed female dog was presented for evaluation of two masses in the right abdominal mammary gland region. Surgery was conducted to excise the masses. A grade I complex mammary gland carcinoma and high grade (grade III) mast cell tumor with an inguinal lymph node metastasis were diagnosed. Forty-seven days after the surgical procedure, the mast cell tumor relapsed, and neoadjuvant treatment with lomustine (81 mg/m2 ) was prescribed. Thirteen days from initiation of lomustine therapy, the dog was re-presented to the hospital with bloody diarrhea, hematemesis, epistaxis, an elevated rectal temperature, depression, severe dehydration, and marked dyspnea. The CBC showed severe thrombocytopenia and leukopenia. According to the owner, lomustine (45mg per os [PO]) was mistakenly administered daily for 10 consecutive days (total dose, 810 mg/m2 ). The dog died and a necropsy was performed. The main gross lesions consisted of severe multifocal hemorrhages in multiple organs, especially in the digestive system. Histopathologic evaluation revealed disseminated hemorrhages, as well as marked bone marrow aplasia. This report describes the clinical, hematologic, gross, and histologic findings in a fatal case of lomustine overdose in a dog.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Carcinoma/tratamento farmacológico , Doenças do Cão/diagnóstico , Transtornos Hemorrágicos/veterinária , Leucopenia/veterinária , Lomustina/efeitos adversos , Trombocitopenia/veterinária , Animais , Antineoplásicos Alquilantes/administração & dosagem , Medula Óssea/patologia , Doenças do Cão/sangue , Doenças do Cão/patologia , Cães , Evolução Fatal , Feminino , Transtornos Hemorrágicos/sangue , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemorrágicos/patologia , Lomustina/administração & dosagem , Metástase Linfática , Glândulas Mamárias Animais/patologia
15.
J Med Econ ; 22(10): 1006-1013, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31050315

RESUMO

Purpose: The EF-14 trial demonstrated that adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) significantly extends progression-free survival (PFS) and overall survival (OS) for newly-diagnosed glioblastoma (GBM) patients. This study assessed the cost-effectiveness of TTFields and TMZ for newly-diagnosed GBM from the US healthcare system perspective. Methods and materials: Outcomes for newly-diagnosed GBM patients were estimated over a lifetime horizon using an area under the curve model with three states: stable disease, progressive disease, or death. The survival model integrated the 5-year EF-14 trial results with long-term GBM epidemiology data and US background mortality rates. Adverse event rates were derived from the EF-14 trial data. Utility values to determine quality-adjusted life-years, adverse event costs, and supportive care costs were obtained from published literature. A 3% discount rate was applied to future costs and outcomes. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability. Results: Treatment with TTFields and TMZ was estimated to result in a mean increase in survival of 1.25 life years (95% credible range [CR] = 0.89-1.67) and 0.96 quality-adjusted life years (QALYs) (95% CR = 0.67-1.30) compared to treatment with TMZ alone. The incremental total cost was $188,637 (95% CR = $145,324-$225,330). The incremental cost-effectiveness ratio (ICER) was $150,452 per life year gained and $197,336 per QALY gained. The model was most sensitive to changes in the cost of TTFields treatment. Conclusions: Adding TTFields to maintenance TMZ resulted in a substantial increase in the estimated mean lifetime survival and quality-adjusted survival for newly-diagnosed GBM patients. Treatment with TTFields can be considered cost-effective within the reported range of willingness-to-pay thresholds in the US.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/economia , Terapia Combinada/economia , Análise Custo-Benefício , Glioblastoma/tratamento farmacológico , Temozolomida/administração & dosagem , Temozolomida/economia , Intervalo Livre de Doença , Glioblastoma/diagnóstico , Humanos
16.
Invest Ophthalmol Vis Sci ; 60(5): 1696-1705, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009525

RESUMO

Purpose: The goal of this work was to design and assess the ability of unmodified and surface-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to enhance cell association, provide efficacy in retinoblastoma cells, and overcome current administration challenges, including hydrolysis and precipitation, of intravitreal administration. Methods: A single emulsion method was used to encapsulate Coumarin 6, to enable NP visualization via fluorescence microscopy. Melphalan NPs were synthesized using an adapted double-emulsion method to reduce melphalan loss during fabrication. Melphalan loading and release were quantified against a free melphalan standard. The cellular association and internalization of unmodified and surface-modified NPs were determined using flow cytometry, and the efficacy of melphalan NPs was quantified in retinoblastoma cells. Results: The highest cell association was observed with TET1 and MPG-NPs after 24 hours administration; however, a significant fraction of NPs were associated with the cell surface, instead of undergoing internalization. MPG-NPs fabricated with the low saturation process were most efficacious, while all surface-modified NPs improved efficacy relative to unmodified NPs when formulated using the highly saturated process. Similar effects were observed as a function of NP dose, with TET1 and MPG-NPs particularly efficacious. Conclusions: Surface-modified NPs achieved enhanced association and efficacy in retinoblastoma cells relative to unmodified NPs, with MPG and surface-modified NPs exhibiting the strongest efficacy relative to other NP groups. In future work we seek to assess the ability of these NPs to improve transport in the vitreous, where we expect a more dramatic impact on efficacy as a function of surface modification.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Melfalan/administração & dosagem , Nanopartículas/química , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Cumarínicos/química , Citometria de Fluxo , Humanos , Injeções Intravítreas , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tiazóis/química , Células Tumorais Cultivadas
17.
Cell Prolif ; 52(3): e12608, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30932251

RESUMO

OBJECTIVES: We performed histological, cellular and behavioural analyses of the effects of cyclophosphamide (CTX), a chemotherapeutic drug, in the developing cerebellum and aimed to provide valuable insights into clinical application of CTX in children. MATERIALS AND METHODS: C57BL/6 mice and Math1-dependent GFP expression transgenic mice were used in the research. H&E staining was performed to analyse histological effects of CTX in the cerebellum. Staining for EdU and TUNEL was used to estimate the cell proliferation and apoptosis. Rotarod test and hanging wire test were used to evaluate the behavioural functions. Immunofluorescent staining was used to identify the cell types. The differentiation markers and genes related to Sonic Hedgehog (SHH) signalling were measured via quantitative real-time PCR or immunoblotting. RESULTS: We found that while CTX induced a significant reduction in cell proliferation and increased apoptosis in the EGL in 48 hours, the behavioural functions and the multilayer laminar structure of cerebella were largely restored when the mice grew to adults. Mechanistically, granule neuron progenitors, driven by the SHH signalling, enhanced the capability of proliferation quickly after CTX administration was stopped, which allowed the developing cerebellum to catch up and to gradually replenish the injury. CONCLUSION: The chemotherapeutic agent CTX induces an immediate damage to the developing cerebellum, but the cerebellar multilayer laminar structure and motor function can be largely restored if the agent is stopped shortly after use.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Ciclofosfamida/efeitos adversos , Animais , Animais Recém-Nascidos , Antineoplásicos Alquilantes/administração & dosagem , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cerebelo/crescimento & desenvolvimento , Cerebelo/patologia , Criança , Ciclofosfamida/administração & dosagem , Proteínas Hedgehog/metabolismo , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Animais , Neurogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
18.
Arch Ital Urol Androl ; 91(1): 49-50, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30932430

RESUMO

Primary urethral lymphoma is a rare entity without a standardized treatment protocol. We report a case of an elderly woman presenting with a caruncle associated with vaginal spotting and intermittent dysuria. She underwent surgical excision of the lesion. Histological analysis revealed a blastoid variant of mantle cell lymphoma, a previously unreported subtype. The patient received chlorambucil assisting a rapid local disease progression. She died of disseminated disease 6 months after diagnosis. A review of the lymphomas of the urethra is included.


Assuntos
Linfoma de Célula do Manto/diagnóstico , Doenças Uretrais/diagnóstico , Neoplasias Uretrais/diagnóstico , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Clorambucila/administração & dosagem , Diagnóstico Diferencial , Progressão da Doença , Disuria/etiologia , Evolução Fatal , Feminino , Humanos , Linfoma de Célula do Manto/patologia , Doenças Uretrais/patologia , Neoplasias Uretrais/patologia
19.
Trends Pharmacol Sci ; 40(5): 342-357, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30979523

RESUMO

Although old molecules, alkylating agents and platinum derivatives are still widely used in the treatment of various solid tumors. However, systemic toxicity and cellular resistance mechanisms impede their efficacy. Innovative strategies, including local administration, optimization of treatment schedule/dosage, synergistic combinations, and the encapsulation of bioactive molecules in smart, multifunctional drug delivery systems, have shown promising results in potentiating anticancer activity while circumventing such hurdles. Furthermore, questioning of the old paradigm according to which nuclear DNA is the critical target of their anticancer activity has shed light on subcellular alternative and neglected targets that obviously participate in the mediation of cytotoxicity or resistance. Thus, rethinking of the use of these pivotal antineoplastic agents appears critical to improve clinical outcomes in the management of solid tumors.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/química , Sistemas de Liberação de Medicamentos , Sinergismo Farmacológico , Humanos
20.
Ophthalmic Surg Lasers Imaging Retina ; 50(4): 248-252, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998248

RESUMO

A 35-month-old boy was diagnosed with retinoblastoma and underwent combination intra-arterial (IAC) and intravitreal chemotherapy. His course was complicated by anaphylactic reaction to IAC, yet he continued to improve with sustained intravitreal therapy. Eight months into treatment, the affected eye developed exudative retinal detachment, which resolved with sub-Tenon's steroid administration. As the management of retinoblastoma evolves, treaters need to be aware of potential complications of therapy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:248-252.].


Assuntos
Melfalan/efeitos adversos , Descolamento Retiniano/induzido quimicamente , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Topotecan/efeitos adversos , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Pré-Escolar , Quimioterapia Combinada , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Injeções Intraoculares , Injeções Intravítreas , Macula Lutea/diagnóstico por imagem , Masculino , Melfalan/administração & dosagem , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/tratamento farmacológico , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Inibidores da Topoisomerase I/administração & dosagem , Inibidores da Topoisomerase I/efeitos adversos , Topotecan/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Ultrassonografia
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