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1.
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
2.
Medicine (Baltimore) ; 99(1): e18663, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895831

RESUMO

BACKGROUND: Radiotherapy concurrent with cisplatin is the standard regimen used for treatment of locally advanced cervical carcinoma. In this meta-analysis, survival, recurrence, compliance, and acute adverse effects were compared between weekly and triweekly cisplatin-based concurrent chemoradiotherapy regimens for treatment of cervical cancer. METHODS: A systematic search for relevant studies was conducted using PubMed, Cochrane Library, EMBASE, and Medline databases. Fixed- or random-effects models were used for pooled analysis. The endpoints were overall survival, recurrence, compliance, and acute adverse effects reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Eight randomized controlled trials met the inclusion criteria. No significant differences were observed between the 2 arms with respect to recurrence, survival, and acute adverse effects (all P > .05). However, the triweekly cisplatin regimen was associated with significantly lower incidence of local recurrence (OR, 1.72; 95% CI, 1.07-2.78; P = .03), radiotherapy completion (OR, 2.08; 95% CI, 0.99-4.38; P = .05), and anemia (OR, 2.10; 95% CI, 1.01-4.37; P = .05), while a weekly cisplatin regimen was associated with a lower risk of leukopenia (OR, 0.57; 95% CI, 0.42-0.92; P = .00) and thrombocytopenia (OR, 0.55; 95% CI, 0.31-0.97; P = .04). CONCLUSIONS: Triweekly cisplatin-based chemotherapy significantly reduced local recurrence with tolerable toxicity and might be the optimal regimen in concurrent chemoradiotherapy for locally advanced cervical carcinoma.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma/terapia , Cisplatino/administração & dosagem , Neoplasias do Colo do Útero/terapia , Quimiorradioterapia , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
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
4.
Dis Colon Rectum ; 63(2): 242-255, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31914116

RESUMO

BACKGROUND: Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment; however, the morbidity is considerable and the survival benefit is modest. Cytoreductive surgery and heated intraperitoneal chemotherapy is a potentially curative treatment available to a minority of patients; however, most develop recurrent disease. A novel palliative treatment for peritoneal metastases, pressurized intraperitoneal aerosol chemotherapy, has recently been introduced. Pressurized intraperitoneal aerosol chemotherapy utilizes an aerosol of chemotherapy in carbon dioxide gas. It is instilled into the abdomen under pressure via laparoscopic ports. No cytoreduction is performed. Pressurized intraperitoneal aerosol chemotherapy can be repeated at 6-week intervals. Oxaliplatin or cis-platinum and doxorubicin have been used to date. OBJECTIVE: This study aims to systematically review and evaluate the method, and the preclinical and early clinical results of pressurized intraperitoneal aerosol chemotherapy. DATA SOURCES: Medline and the Cochrane Library were the data sources for the study. STUDY SELECTION: Peer-reviewed series of greater than 10 patients, with sufficient patient data, through April 2019, were selected. INTERVENTION: Patients with peritoneal metastases underwent pressurized intraperitoneal aerosol chemotherapy. MAIN OUTCOME MEASURES: Patient dropout, histologic tumor response, adverse events, and 30-day mortality were the primary outcomes measured. RESULTS: A total of 921 patients with peritoneal metastases were brought to the operating room for pressurized intraperitoneal aerosol chemotherapy. The number of pressurized intraperitoneal aerosol chemotherapy treatments administered was as follows: 1 treatment, 862 (94%); 2 treatments, 645 (70%); and 3 treatments, 390 patients (42%). Initial laparoscopic access was not possible in 59 patients (6.4%). Common Terminology Criteria for Adverse Events grade 3 or higher were noted in 13.7% of the patients who, collectively, underwent a total of 2116 treatments. The 30-day mortality was 2.4% (22/921). LIMITATIONS: This study was limited by the heterogeneity of reported data and primary tumor types and by the lack of long-term survival data. CONCLUSIONS: Early clinical results are encouraging, but tumor-specific, prospective, randomized trials are needed to compare pressurized intraperitoneal aerosol chemotherapy to systemic chemotherapy. This method has yet to be introduced to the United States. It is another therapeutic option for patients with peritoneal metastases and will broaden the patient base for future clinical trials.


Assuntos
Aerossóis/administração & dosagem , Cuidados Paliativos/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Aerossóis/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dióxido de Carbono/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Humanos , Hipertermia Induzida/métodos , Instilação de Medicamentos , Laparoscopia/métodos , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/mortalidade , Pressão , Resultado do Tratamento
5.
Gynecol Oncol ; 156(1): 13-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708167

RESUMO

BACKGROUND: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. METHODS: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. FINDINGS: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. INTERPRETATION: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). FUNDING: National Cancer Institute.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Epitelial do Ovário/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Peritoneais/patologia , Intervalo Livre de Progressão
6.
Gynecol Oncol ; 156(1): 100-106, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31810653

RESUMO

OBJECTIVES: Chemotherapy is the standard treatment in stage IVB cervical cancer (CC). However, given that many women have a significant pelvic disease burden, whole pelvic radiation (WPR) in addition to chemotherapy for primary treatment may have utility. The aim of this study was to compare the overall survival (OS) and complication rates between women who received both WPR and chemotherapy (CT) versus CT alone in the management of stage IVB CC. METHODS: A multi-institutional, IRB-approved, retrospective review of patients (pts) with stage IVB CC, diagnosed between 2005 and 2015, was performed. Descriptive statistics of the demographic, oncologic, and treatment characteristics were performed. OS was estimated using the Kaplan Meier method. RESULTS: A total of 126 pts met inclusion criteria. Thirty one patients elected for hospice care at diagnosis and were excluded from further analysis. In the remaining population, median age was 53 yrs. The majority (72%) had squamous cell carcinoma and 82% had FIGO grade 2 or 3 tumors. Thirty four patients (35.8%) received WPR in addition to CT as a part of planned primary therapy and 64.2% (n = 61) received CT alone, with 88.2% and 80.3% receiving a cisplatin-based chemotherapy regimen, respectively. The OS was significantly longer in the WPR with CT group (41.6 vs 17.6 mo, p < 0.01). The rates of ureteral obstruction, vaginal bleeding, pelvic infection, pelvic pain, and fistula were not significantly different between the 2 groups (all p > 0.05). CONCLUSION: This study found WPR in addition to CT gives a significant OS benefit. Further study is warranted to determine which subgroups may benefit the most from this novel treatment strategy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Cisplatino/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Pelve/efeitos da radiação , Intervalo Livre de Progressão , Radioterapia/métodos , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias do Colo do Útero/patologia , Adulto Jovem
8.
Oncology ; 98(1): 48-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31487733

RESUMO

INTRODUCTION: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer (GC) with peritoneal metastasis (PM). Recently, superiority of IP administration of paclitaxel (PTX) combined with S-1 and intravenous PTX over conventional systemic chemotherapy was suggested in a phase III study, although the difference in overall survival did not reach statistical significance in the primary analysis. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy are warranted. We designed a new regimen combining IP PTX with S-1 plus cisplatin (SP), which is regarded as the standard first-line treatment for metastatic GC in Japan, and subsequently carried out a dose-escalation study. METHODS: The combination was a 5-weekly regimen. IP PTX was to be administered on days 1, 8, and 22 with an initial dose of 15 mg/m2 at level 1 and 20 mg/m2 at level 2. S-1 was to be administered orally at a fixed dose of 80 mg/m2 b.i.d. for 21 days followed by a -14-day rest. Cisplatin was to be administered intravenously at a dose of 60 mg/m2 on day 8. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 (G3) febrile neutropenia, G3 thrombocytopenia, and G3 nonhematological toxicity. RESULTS: A total of 9 patients with macroscopic PM were enrolled. No DLTs were observed among the 3 patients at level 1 and 6 patients at level 2. No adverse events or technical problems associated with the IP administration were observed. Consequently, the maximum-tolerated dose was not reached, and the dose for further clinical trials of IP PTX was determined as 20 mg/m2. As for efficacy, peritoneal lavage cytology turned negative after the first course in 4 of 7 patients who had positive cytology before treatment. CONCLUSION: The present study determined the dose for further clinical trials of IP PTX to be 20 mg/m2, when combined with the 5-weekly SP regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Resultado do Tratamento
9.
J Cancer Res Clin Oncol ; 146(1): 33-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31728618

RESUMO

PURPOSE: Concurrent chemoradiotherapy (CCRT) is one of the standard treatments for patients with advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT may lead to decreased quality of life (QoL) and treatment compliance. This study aimed to determine the effects of PG2 (Astragalus polysaccharides) injection on CCRT-associated adverse events (AEs) and patients' compliance with the CCRT course. METHODS: In this phase II double-blind randomized placebo-controlled trial, PG2 injection (sterile powder form) or placebo was administrated three times per week in parallel with CCRT to patients with HNSCC. The chemotherapy regimen included 50 mg/m2 cisplatin every 2 weeks with daily tegafur-uracil (300 mg/m2) and leucovorin (60 mg/day). RESULTS: The study was terminated prematurely due to the successful launch of a newly formulated PG2 injection (lyophilized form). A total of 17 patients were enrolled. The baseline demographics and therapeutic compliance were comparable between the CCRT/PG2 and CCRT/placebo groups. During CCRT, severe treatment-associated AEs were less frequent in the CCRT/PG2 group than in the CCRT/placebo group. Furthermore, less QoL fluctuations from the baseline during CCRT were noted in the CCRT/PG2 group than in the CCRT/placebo group, with a significant difference in the pain, appetite loss, and social eating behavior. The tumor response, disease-specific survival and overall survival did not differ between the two groups. CONCLUSION: This preliminary study demonstrated PG2 injection exhibited an excellent safety profile, and has potential in ameliorating the deterioration in QoL and the AEs associated with active anticancer treatment among patients with advanced pharyngeal or laryngeal HNSCC under CCRT. Further research in patients with other cancer types or treatment modalities may widen PG2's application in clinical settings.


Assuntos
Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/radioterapia , Polissacarídeos/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Astrágalo (Planta) , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Tegafur/administração & dosagem , Uracila/administração & dosagem
10.
J Cancer Res Clin Oncol ; 146(2): 477-483, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31686249

RESUMO

OBJECTIVE: To evaluate treatment outcomes after definitive chemoradiotherapy (CRT) for human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: We analyzed data concerning HPV-negative OPSCC patients treated with curative intent. All patients received concomitant high-dose cisplatin-based chemotherapy. Two different RT techniques were used: (1) sequential boost IMRT (S-IMRT) to a total dose of 70 Gy (2 Gy/fraction); (2) simultaneously integrated boost (SIB-IMRT) to a total dose of 67.5 Gy (2.25 Gy/fraction). Survival outcomes were estimated. RESULTS: In total, 69 HPV-negative OPSCC patients were included (n = 40 S-IMRT; n = 29 SIB-IMRT). The median follow-up time was 40 months. The 3-year overall survival, disease-free survival, distant metastasis-free survival and locoregional-free survival were 67.1%, 63.3%, 64.5% and 66.0%, respectively. Alcohol abuse and advanced stage disease at presentation were the main risk factors for worse survival outcomes. Complete clinical response (cCR) at 3 months after CRT improved overall survival (86.3% versus 42.5%, p < 0.01). The cCR events were greater but not statistically significant in SIB-IMRT group compared to S-IMRT patients (69% versus 47.5%, p = 0.09). CONCLUSIONS: The positive impact of cCR at 3 months on survival needs to be confirmed in randomized clinical trials, as well as its close correlation with SIB-IMRT technique. A proper stratification of HPV-negative OPSCC patients should be paramount to tailor treatment strategy in the near future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Quimiorradioterapia , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida , Resultado do Tratamento
12.
Carbohydr Polym ; 227: 115333, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590864

RESUMO

The gold nanoparticles surface was modified by thioglycolic acid ligand and their surface was coated by the chitosan-grafted-poly(N-vinylcaprolactam) (chitosan-g-PNVCL) copolymer. The cisplatin anticancer drug was loaded into the synthesized nanocarriers and its performance was investigated for the treatment of MCF-7 breast cancer cells in vitro. The synthesized nanoparticles were characterized using FTIR, DLS, TEM, SEM, EDX and TGA analysis. The lower critical solution temperature (LCST) of PNVCL/chitosan and PNVCL/chitosan coated gold nanoparticles were found to be 38 and 39 °C, respectively. The cisplatin loading efficiency, cisplatin release from nanoparticles at different temperatures and pH values as well as the pharmacokinetic studies were examined. The maximum cisplatin release from nanoparticles was achieved at T > LCST (42 °C) and pH of 5. The Korsemeyer-Peppas model was best described the cisplatin release from nanoparticles. The maximum MCF cell death was found to be 92% using cisplatin loaded-gold/TGA/chitosan-g-PNVCL nanoparticles under an induction heating system.


Assuntos
Antineoplásicos , Caprolactama/análogos & derivados , Quitosana , Cisplatino , Ouro , Nanopartículas Metálicas , Polímeros , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Caprolactama/administração & dosagem , Caprolactama/química , Caprolactama/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Quitosana/administração & dosagem , Quitosana/química , Quitosana/farmacocinética , Cisplatino/administração & dosagem , Cisplatino/química , Cisplatino/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Ouro/administração & dosagem , Ouro/química , Humanos , Células MCF-7 , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacocinética
13.
Br J Radiol ; 93(1106): 20180781, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860336

RESUMO

OBJECTIVE: The aim of the study was to assess the feasibility of multitracer positron emission tomography (PET) imaging before and during chemoradiation and to evaluate the predictive value of image-based factors for outcome in locally advanced head and neck cancers treated with chemoradiation. METHODS: In the week prior to the treatment [18F]-2-flu-2-deoxy-D-glucose (FDG), [18F]-3'-flu-3'deoxythymidine (FLT) and [18F]-flumisonidazole (FMISO) imaging was performed. FLT scans were repeated at 14 and 28 Gy and FMISO at 36 Gy. Overall survival, disease-free survival and local control were correlated with subvolume parameters, and with tumour-to-muscle ratio for FMISO. For every tracer, total metabolic tumour volume was calculated. RESULTS: 33 patients were included. No correlation was found between pre-treatment maximum standardised uptake value for FDG, FLT, FMISO and outcomes. Tumour volume measured on initial CT scans and initial FLT volume correlated with disease-free survivall (p = 0.007 and 0.04 respectively). FDG and FLT metabolic tumour volumes correlated significantly with local control (p = 0.005 and 0.02 respectively). In multivariate Cox analysis only individual initial TMRmax correlated with overall survival. CONCLUSION: PET/CT imaging is a promising tool. However, various aspects of image analysis need further clinical validation in larger multicentre study employing uniform imaging protocol and standardisation, especially for hypoxia tracer. ADVANCES IN KNOWLEDGE: Monitoring of biological features of the tumour using multitracer PET modality seems to be a feasible option in daily clinical practice.Evaluation of hypoxic subvolumes is more patient dependent; thus, exploration of individual parameters of hypoxia is needed. tumour-to-muscle ratio seems to be the most promising so far.


Assuntos
Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Didesoxinucleosídeos/metabolismo , Intervalo Livre de Doença , Esquema de Medicação , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18/metabolismo , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Misonidazol/análogos & derivados , Misonidazol/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Radiossensibilizantes/metabolismo , Resultado do Tratamento , Hipóxia Tumoral/efeitos dos fármacos
14.
Int J Cancer ; 146(2): 413-423, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31246277

RESUMO

In the OS2006 study, patients younger than 18 years were treated with a methotrexate-based regimen (MTX), patients older than 25 years with a doxorubicin-cisplatin-ifosfamide-based regimen (API-AI), whereas patients aged 18-25 years received either API-AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API-AI. Preoperative chemotherapy combined three doxorubicin-ifosfamide-cisplatin (API) and two doxorubicin-ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin-ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide-ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18-67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety-six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28-48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow-up of 4.8 years, the 5-year event-free survival and overall survival rates were 46% (95% CI 36-56) and 57% (95% CI 47-67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API-AI proved feasible with no excess of toxicity, and favourable activity despite poor-prognosis factors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/terapia , Osteossarcoma/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Estudos de Viabilidade , Feminino , Seguimentos , França/epidemiologia , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem , Ácido Zoledrônico/administração & dosagem , Ácido Zoledrônico/efeitos adversos
15.
Anticancer Res ; 39(12): 6819-6827, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810948

RESUMO

BACKGROUND/AIM: This Japanese multiple-center retrospective study aimed to examine the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: A total of 100 R/M SCCHN patients treated with the EXTREME regimen as first-line therapy were analyzed. The treatment outcomes were evaluated to compare patient and treatment characteristics with overall survival. RESULTS: Patients treated with carboplatin-based EXTREME regimen showed similar overall survival with less adverse effects compared to that of patients using cisplatin. The post-progression survival was significantly longer in patients treated with second-line treatment following the EXTREME regimen than in those without second-line treatment. CONCLUSION: The carboplatin-based EXTREME regimen was more feasible with similar treatment outcomes compared to cisplatin-based EXTREME regimen. In addition, subsequent lines of therapy contributed to improvement of survival for R/M SCCHN patients.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
16.
J Exp Ther Oncol ; 13(2): 131-138, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31881129

RESUMO

Background: Continuation maintenance therapy with pemetrexed (PEM) and bevacizumab (BEV) following induction therapy with cisplatin (CDDP), PEM, and BEV is beneficial in advanced non-squamous non-small-cell lung cancer (NS-NSCLC), but the survival benefit of addition of BEV to CDDP/PEM as induction therapy is still unclear. The aim of this phase II study was to evaluate the feasibility and safety of a CDDP/PEM/BEV regimen in Japanese patients with EGFR wild-type NS-NSCLC. Patients and Methods: This study included 25 patients who receive intravenous CDDP, PEM, and BEV (15 mg/kg) from August 2010 to February 2013. The primary endpoint of this study was the response rate (RR) and the secondary endpoint was progression free survival (PFS), overall survival (OS), and safety. Results: The median cycles of induction chemotherapy were four (range 1-6). RR was 64%. Most patients (64%) transitioned to maintenance therapy. The median PFS was 9.7 months. Median OS was 21.6 months. Haematological adverse events reaching grade 3 to 4 were neutropenia (8%) without febrile neutropenia, thrombocytopenia (4%), and anemia (4%). BEV-related non-haematological toxicities of grade 3/4 were hypertension (16%), thrombosis (4%), and gastrointestinal perforation (4%). Each adverse events was controllable, and there were no treatment-related deaths. Conclusions: CDDP/PEM/BEV regimen is effective and tolerable in patients with EGFR wild-type advanced NS-NSCLC, but should be paid attention to some BEV-related toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/administração & dosagem , Receptores ErbB , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Resultado do Tratamento
17.
Pharm Res ; 36(12): 182, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741089

RESUMO

PURPOSE: Combination chemotherapy is gradually receiving more attention because of its potential synergistic effect and reduced drug doses in clinical application. However, how to precisely control drug release dose and time using vehicles remains a challenge. This work developed an efficient drug delivery system to combat breast cancer, which can enhance drug effects despite reducing its concentration. METHODS: Controlled-release poly-lactic-co-glycolic acid (PLGA) scaffolds were fabricated by E-jet 3D printing to deliver doxorubicin (DOX) and cisplatin (CDDP) simultaneously. RESULTS: This drug delivery system allowed the use of a reduced drug dosage resulting in a better effect on the human breast cancer cell apoptosis and inhibiting tumor growth, compared with the effect of each drug and the two drugs administrated without PLGA scaffolds. Our study suggested that DOX-CDDP-PLGA scaffolds could efficiently destroy MDA-MB-231 cells and restrain tumor growth. CONCLUSIONS: The 3D printed PLGA scaffolds with their time-programmed drug release might be useful as a new multi-drug delivery vehicle in cancer therapy, which has a potential advantage in a long term tumor cure and prevention of tumor recurrence.


Assuntos
Antineoplásicos/química , Cisplatino/química , Doxorrubicina/química , Portadores de Fármacos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Quimioterapia Combinada/métodos , Excipientes/química , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Impressão Tridimensional
18.
Adv Clin Exp Med ; 28(11): 1537-1543, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31766081

RESUMO

BACKGROUND: Cisplatin, used in cancer treatment, has toxic and apoptotic effects on the peripheral nervous system. Rutin, also known as vitamin P, has antioxidant and antiapoptotic activity. OBJECTIVES: The purpose of this study was to investigate the biochemical and histopathologic efficacy of rutin on neurotoxic and apoptotic effects caused by cisplatin in the peripheral nervous system. MATERIAL AND METHODS: Twenty-four albino Wistar male rats were divided into the following 4 groups: control group (CG), only cisplatin-injected group (CIS), cisplatin and rutin 50 mg/kg (RG-50)-injected group, and cisplatin and rutin 100 mg/kg (RG-100)-injected group. Analyses were performed on sciatic nerve tissue of experimental animals. Analyses of malondialdehyde (MDA), total glutathione (tGSH), glutathione reductase (GSHRd), glutathione-s-transferase (GST), and superoxide dismutase (SOD) were performed. Caspase-3 expression in nerve tissue was also investigated. The analyzed groups were compared with CG. RESULTS: Biochemical investigation shows that there is a statistically significant difference between CG and only CIS and RG-50. Control group and RG-100 were found to be similar. Cisplatin-induced changes were observed in histopathological analysis of the nerve tissue. The RG-100 and CG were found to be similar. The caspase-3 expression in the neural tissue was compared between groups. Control group and CIS were found to be different. Control group and RG-100 were found to be similar. CONCLUSIONS: Antioxidant and antiapoptotic effectiveness of rutin was detected against the toxic effects caused by cisplatin in the peripheral nerve tissue.


Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Cisplatino/efeitos adversos , Tecido Nervoso/efeitos dos fármacos , Rutina/farmacologia , Animais , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Rutina/uso terapêutico , Superóxido Dismutase/metabolismo
19.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704853

RESUMO

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/enzimologia , Mesotelioma/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/análise , Neoplasias Pleurais/enzimologia , Serina-Treonina Quinases TOR/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Pemetrexede/administração & dosagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Pneumonectomia , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
20.
Crit Rev Oncol Hematol ; 143: 130-138, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31634730

RESUMO

Germ cell tumors (GCTs) are the most common type of solid tumor amongst patients between 15 and 35 years of age. They are also one of the types of tumor with the highest cure rate, due to their high sensitivity to cisplatin based chemotherapy. Nonetheless, around 15-20% of metastatic patients will not have curative options after a relapse on the first and second line. This proves that new therapeutic options for these refractory GCTs patients need to be developed. This article offers a bibliographic review of all studies using targeted treatment or immunotherapy for refractory GCTs patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Humanos , Masculino , Terapia de Alvo Molecular , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/tratamento farmacológico , Seminoma/patologia , Teratoma/tratamento farmacológico , Teratoma/patologia , Neoplasias Testiculares/patologia , Adulto Jovem
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