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[PMID]:29298350
[Au] Autor:Tatsuta T; Satoh T; Sugawara S; Hara A; Hosono M
[Ad] Endereço:Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Aobaku, Sendai, Japan.
[Ti] Título:Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo.
[So] Source:PLoS One;13(1):e0190653, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malignant mesothelioma is an aggressive cancer that results from exposure to asbestos. The therapeutic options for this type of cancer are limited; therefore, the development of novel therapeutic agents is urgently required. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a novel therapeutic candidate for cancer, which exhibits antitumor activity mediated through RNA degradation. In the present study, we evaluated the effect of cSBL in vitro and in vivo. Xenograft-competent H2452 and MSTO human mesothelioma cell lines were treated with cSBL, and the pathway by which cSBL induces apoptosis was analyzed. In vivo studies were performed using nude mice inoculated with one of the two cell lines, and the effects of cSBL and pemetrexed were monitored simultaneously. Furthermore, the pharmacological interactions between the three agents (pemetrexed, cisplatin and cSBL) were statistically assessed. It was demonstrated that cSBL treatments caused morphological and biochemical apoptotic changes in both cell lines. Caspase cascade analysis revealed that an intrinsic pathway mediated cSBL-induced apoptosis. The administration of cSBL significantly inhibited tumor growth in two xenograft models, without any adverse effects. Furthermore, the combination index and dose reduction index values indicated that the cSBL + pemetrexed combination showed the highest synergism, and thus potential for reducing dosage of each drug, compared with the other combinations, including the existing pemetrexed + cisplatin regimen. cSBL exerted prominent antitumor effects on malignant mesothelioma cells in vitro and in vivo, and showed favorable effects when combined with pemetrexed. These results suggest that cSBL has potential as a novel drug for the treatment of malignant mesothelioma.
[Mh] Termos MeSH primário: Proteínas de Anfíbios/farmacologia
Proliferação Celular/efeitos dos fármacos
Lectinas/farmacologia
Mesotelioma/patologia
Óvulo/química
Ribonucleases/farmacologia
[Mh] Termos MeSH secundário: Proteínas de Anfíbios/isolamento & purificação
Animais
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Sinergismo Farmacológico
Feminino
Seres Humanos
Técnicas In Vitro
Lectinas/isolamento & purificação
Masculino
Camundongos Endogâmicos BALB C
Camundongos Nus
Pemetrexede/administração & dosagem
Rana catesbeiana
Ribonucleases/isolamento & purificação
Perda de Peso/efeitos dos fármacos
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amphibian Proteins); 0 (Lectins); 04Q9AIZ7NO (Pemetrexed); EC 3.1.- (Ribonucleases); EC 3.1.- (leczyme protein, Rana)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190653


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[PMID]:29310415
[Au] Autor:Abramavicius S; Zemaitis M; Pilvinis V; Kadusevicius E
[Ad] Endereço:Institute of Physiology and Pharmacology.
[Ti] Título:Cisplatin-induced sudden cardiac death with hemodynamic collapse: a severe adverse drug reaction: Case report.
[So] Source:Medicine (Baltimore);96(48):e8995, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Cisplatin is responsible for a significant percentage of adverse drug reactions (ADRs) in oncology setting. A great proportion of cisplatin-induced severe adverse events are difficult to foresee, and giving premedication does not always prevent the occurrence of such events. PATIENT CONCERNS: A 53-year-old woman with progressive T4 N0 M0 stage IV pleural mesothelioma experienced cardiac arrest with hemodynamic collapse after cisplatin and pemetrexed chemotherapy administration. DIAGNOSES: Progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung, primary arterial hypertension, and cardiac arrest with hemodynamic collapse. INTERVENTIONS: The cisplatin and pemetrexed chemotherapy was administered intravenously for progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung. During infusion of cisplatin the patient developed cardiac arrest, and cardiopulmonary resuscitation was initiated. OUTCOMES: The patient was treated in intensive care unit and recovered successfully. Further chemotherapy with cisplatin and pemetrexed was withheld due to this severe adverse reaction to cisplatin. LESSONS: Cisplatin therapy should be thoroughly monitored including electrolyte, especially magnesium levels. Absence of previous ADRs to cisplatin and premedication should not give false sense of security.
[Mh] Termos MeSH primário: Antineoplásicos/efeitos adversos
Cisplatino/efeitos adversos
Morte Súbita Cardíaca/etiologia
[Mh] Termos MeSH secundário: Antineoplásicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Cisplatino/uso terapêutico
Feminino
Seres Humanos
Neoplasias Pulmonares/tratamento farmacológico
Mesotelioma/tratamento farmacológico
Meia-Idade
Pemetrexede/uso terapêutico
Neoplasias Pleurais/tratamento farmacológico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 04Q9AIZ7NO (Pemetrexed); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008995


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[PMID]:28950288
[Au] Autor:Greystoke A; Steele N; Arkenau HT; Blackhall F; Md Haris N; Lindsay CR; Califano R; Voskoboynik M; Summers Y; So K; Ghiorghiu D; Dymond AW; Hossack S; Plummer R; Dean E
[Ad] Endereço:Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK.
[Ti] Título:SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting.
[So] Source:Br J Cancer;117(7):938-946, 2017 Sep 26.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We investigated selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective, allosteric MEK1/2 inhibitor, plus platinum-doublet chemotherapy for patients with advanced/metastatic non-small cell lung cancer. METHODS: In this Phase I, open-label study (NCT01809210), treatment-naïve patients received selumetinib (50, 75, 100 mg BID PO) plus standard doses of gemcitabine or pemetrexed plus cisplatin or carboplatin. Primary objectives were safety, tolerability, and determination of recommended Phase II doses. RESULTS: Fifty-five patients received treatment: selumetinib 50 or 75 mg plus gemcitabine/cisplatin (n=10); selumetinib 50 mg plus gemcitabine/carboplatin (n=9); selumetinib 50, 75 or 100 mg plus pemetrexed/carboplatin (n=21); selumetinib 75 mg plus pemetrexed/cisplatin (n=15). Most frequent adverse events (AEs) were fatigue, nausea, diarrhoea and vomiting. Grade ⩾3 selumetinib-related AEs were reported in 30 (55%) patients. Dose-limiting toxicities (all n=1) were Grade 4 anaemia (selumetinib 75 mg plus gemcitabine/cisplatin), Grade 4 thrombocytopenia/epistaxis and Grade 4 thrombocytopenia (selumetinib 50 mg plus gemcitabine/carboplatin), Grade 4 febrile neutropenia (selumetinib 100 mg plus pemetrexed/carboplatin), and Grade 3 lethargy (selumetinib 75 mg plus pemetrexed/cisplatin). Partial responses were confirmed in 11 (20%) and unconfirmed in 9 (16%) patients. CONCLUSIONS: Standard doses of pemetrexed/carboplatin or pemetrexed/cisplatin were tolerated with selumetinib 75 mg BID. The selumetinib plus gemcitabine-containing regimens were not tolerated.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Anemia/induzido quimicamente
Benzimidazóis/administração & dosagem
Benzimidazóis/efeitos adversos
Carboplatina/administração & dosagem
Neutropenia Febril Induzida por Quimioterapia/etiologia
Cisplatino/administração & dosagem
Desoxicitidina/administração & dosagem
Desoxicitidina/análogos & derivados
Diarreia/induzido quimicamente
Epistaxe/induzido quimicamente
Fadiga/induzido quimicamente
Feminino
Seres Humanos
Letargia/induzido quimicamente
Masculino
Meia-Idade
Náusea/induzido quimicamente
Pemetrexede/administração & dosagem
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/efeitos adversos
Trombocitopenia/induzido quimicamente
Vômito/induzido quimicamente
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (AZD 6244); 0 (Benzimidazoles); 0 (Protein Kinase Inhibitors); 04Q9AIZ7NO (Pemetrexed); 0W860991D6 (Deoxycytidine); B76N6SBZ8R (gemcitabine); BG3F62OND5 (Carboplatin); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.271


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[PMID]:28892431
[Au] Autor:Grosso F; Steele N; Novello S; Nowak AK; Popat S; Greillier L; John T; Leighl NB; Reck M; Taylor P; Planchard D; Sørensen JB; Socinski MA; von Wangenheim U; Loembé AB; Barrueco J; Morsli N; Scagliotti G
[Ad] Endereço:Federica Grosso, Azienda Ospedaliera SS Antonio e Biagio General Hospital, Alessandria; Silvia Novello and Giorgio Scagliotti, L'università di Torino, Azienda Sanitaria Ospedale San Luigi Gonzaga, Turin, Italy; Anna K. Nowak, University of Western Australia, Crawley, and Sir Charles Gairdner Hospita
[Ti] Título:Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial.
[So] Source:J Clin Oncol;35(31):3591-3600, 2017 Nov 01.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory phase III part of the study is ongoing.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Pulmonares/tratamento farmacológico
Mesotelioma/tratamento farmacológico
Neoplasias Pleurais/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Cisplatino/administração & dosagem
Intervalo Livre de Doença
Método Duplo-Cego
Feminino
Seres Humanos
Indóis/administração & dosagem
Masculino
Meia-Idade
Pemetrexede/administração & dosagem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Indoles); 04Q9AIZ7NO (Pemetrexed); G6HRD2P839 (nintedanib); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2017.72.9012


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[PMID]:28863158
[Au] Autor:Zhao X; Kong F; Wang L; Zhang H
[Ad] Endereço:Department of Ophthalmology, the Second Hospital of Shandong University, Jinan, Shandong Province, China.
[Ti] Título:c-FLIP and the NOXA/Mcl-1 axis participate in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells.
[So] Source:PLoS One;12(9):e0184135, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Choroidal melanoma is the most common primary malignant intraocular tumor, and very few effective therapies are available to treat it. Our study aimed to understand whether pemetrexed plus cisplatin exerts a beneficial synergistic effect in human choroidal melanoma cells and to delineate the underlying molecular mechanism. To accomplish these aims, we treated choroidal melanoma cells with pemetrexed and cisplatin and assessed cell survival with SRB and MTT assays. Proteins were detected using western blotting analysis. NOXA and CHOP were knocked down with siRNA. We found that pemetrexed or cisplatin alone inhibited survival and induced apoptosis in human choroidal melanoma cells. Furthermore, the expression levels of c-FLIP, an anti-apoptotic protein in the extrinsic apoptosis pathway, and Mcl-1, an anti-apoptotic protein in the intrinsic apoptosis pathway, were decreased by pemetrexed or cisplatin respectively, while the expression of a pro-apoptotic protein in the intrinsic apoptosis pathway, NOXA, was up-regulated. Moreover, pemetrexed or cisplatin alone increased the protein expression of the endoplasmic reticulum stress markers IRE1α, Bip and CHOP. Silencing CHOP expression reduced NOXA expression. These findings suggest that the pemetrexed or cisplatin induced intrinsic apoptosis via activation of the ER stress response. Importantly, combining the two compounds more strongly induced apoptosis. Following the cotreatment, CHOP and NOXA expression increased, while c-FLIP and Mcl-1 expression decreased, and these effects were more pronounced than when using either compound alone. This result suggests that pemetrexed and cisplatin synergistically activate ER stress response-induced apoptosis in choroidal melanoma cells. To summarize, the c-FLIP and NOXA/Mcl-1 axis participated in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells. Intrinsic apoptosis was induced via activation of the ER stress response. Our study provides important mechanistic insights into potential cancer treatment with pemetrexed plus cisplatin and enriches our understanding of human choroidal melanoma.
[Mh] Termos MeSH primário: Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo
Neoplasias da Coroide/tratamento farmacológico
Cisplatino/administração & dosagem
Melanoma/tratamento farmacológico
Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo
Pemetrexede/administração & dosagem
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Apoptose
Linhagem Celular Tumoral
Sobrevivência Celular
Neoplasias da Coroide/metabolismo
Relação Dose-Resposta a Droga
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Melanoma/metabolismo
RNA Interferente Pequeno/metabolismo
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CASP8 and FADD-Like Apoptosis Regulating Protein); 0 (CFLAR protein, human); 0 (MCL1 protein, human); 0 (Myeloid Cell Leukemia Sequence 1 Protein); 0 (PMAIP1 protein, human); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (RNA, Small Interfering); 04Q9AIZ7NO (Pemetrexed); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184135


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[PMID]:28816950
[Au] Autor:Xu T; Wu H; Jin S; Min H; Zhang Z; Shu Y; Wen W; Guo R
[Ad] Endereço:aDepartment of Oncology, the First Affiliated Hospital of Nanjing Medical University bCancer Center of Nanjing Medical University cDepartment of Geriatrics dDepartment of Pathology eDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
[Ti] Título:Pemetrexed-carboplatin with intercalated icotinib in the treatment of patient with advanced EGFR wild-type lung adenocarcinoma: A case report.
[So] Source:Medicine (Baltimore);96(33):e7732, 2017 Aug.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. PATIENT CONCERNS: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. DIAGNOSES: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib. INTERVENTIONS: In this case, we reported the successful long-term maintenance treatment of a patient with EGFR wt NSCLC with pemetrexed and Icotinib. The patient (40-year-old female) was found with ovarian masses and lung masses. Pathological, immunohistochemical, and amplification refractory mutation system (ARMS) assay examinations of ovarian specimen suggested the expression of metastatic lung adenocarcinoma with wt EGFR. After failure treatment with paclitaxel-carboplatin, the patient received 4 cycles of pemetrexed plus platinum with intercalated icotinib and then remained on pemetrexed and icotinib. OUTCOMES: A partial response was achieved after the treatment. The patient's condition had remained stable on pemetrexed and icotinib for more than 20 months, with no evidence of progression. LESSONS: To our knowledge, this is the first report using the long-term maintenance treatment with pemetrexed and intercalated icotinib in EGFR wt patient. The therapeutic strategies warrant further exploration in selected populations of NSCLC.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Receptor do Fator de Crescimento Epidérmico/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/genética
Adenocarcinoma/patologia
Adulto
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Carboplatina/uso terapêutico
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/patologia
Éteres de Coroa/uso terapêutico
Progressão da Doença
Feminino
Seres Humanos
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Neoplasias Ovarianas/secundário
Pemetrexede/uso terapêutico
Proteínas Tirosina Quinases/antagonistas & inibidores
Quinazolinas/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Crown Ethers); 0 (Quinazolines); 04Q9AIZ7NO (Pemetrexed); 9G6U5L461Q (icotinib); BG3F62OND5 (Carboplatin); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007732


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[PMID]:28762849
[Au] Autor:Spigel DR; Mekhail TM; Waterhouse D; Hadley T; Webb C; Burris HA; Hainsworth JD; Greco FA
[Ad] Endereço:a Sarah Cannon Research Institute/Tennessee Oncology, PLLC , Nashville , Tennessee , USA.
[Ti] Título:First-Line Carboplatin, Pemetrexed, and Panitumumab in Patients with Advanced Non-Squamous KRAS Wild Type (WT) Non-Small-Cell Lung Cancer (NSCLC).
[So] Source:Cancer Invest;35(8):541-546, 2017 Sep 14.
[Is] ISSN:1532-4192
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We added panitumumab to standard combination chemotherapy as first-line treatment for patients with advanced KRAS WT non-squamous NSCLC. METHODS: Patients received panitumumab 9 mg/kg IV, pemetrexed 500 mg/m IV, and carboplatin AUC = 6 IV every 21 days. After 6 cycles, maintenance therapy with panitumumab and pemetrexed was administered every 21 days until progressive disease or unacceptable toxicity. RESULTS: 29 of 66 patients (44%) had objective responses. The median TTP was 6 months; median overall survival (OS) was 17 months. Panitumumab increased treatment-related toxicity, notably skin rash. CONCLUSIONS: The addition of panitumumab increased toxicity, and had no discernible impact on efficacy.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Carboplatina/administração & dosagem
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Pemetrexede/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anticorpos Monoclonais/efeitos adversos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Carboplatina/efeitos adversos
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/patologia
Esquema de Medicação
Feminino
Seres Humanos
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Masculino
Meia-Idade
Pemetrexede/efeitos adversos
Proteínas Proto-Oncogênicas p21(ras)/genética
Análise de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (KRAS protein, human); 04Q9AIZ7NO (Pemetrexed); 6A901E312A (panitumumab); BG3F62OND5 (Carboplatin); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1080/07357907.2017.1344698


  8 / 1655 MEDLINE  
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[PMID]:28739776
[Au] Autor:He Q; Bi X; Ren C; Wang Y; Zou P; Zhang H; Chi N; Xiu C; Wang Y; Tao R
[Ad] Endereço:Department of Neurosurgery, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, P.R. China.
[Ti] Título:Phase II Study of the Efficacy and Safety of High-dose Pemetrexed in Combination with Cisplatin Temozolomide for the Treatment of Non-small Cell Lung Cancer with Brain Metastases.
[So] Source:Anticancer Res;37(8):4711-4716, 2017 08.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to explore the efficacy and safety of high-dose pemetrexed with cisplatin versus combination with temozolomide in patients with brain metastases (BM) of lung adenocarcinoma. After standard whole-brain radiotherapy (WBRT, 30 Gy/10 fractions), patients with BM of non-small cell lung cancer (NSCLC) were given high-dose pemetrexed (900 mg/m ) on day 1 of each cycle (3 weeks), and cisplatin was administered on days 1-3 in the cisplatin-treated group. The temozolomide-treated group was treated as follows: 75 mg/m temozolomide orally with concurrent WBRT followed by 150 mg/m temozolomide on days 1-5 with high-dose pemetrexed (900 mg/m ) on day 1 of each cycle (3 weeks). Six cycles later, high-dose pemetrexed (900 mg/m ) monotherapy or the best available supportive therapy was administered to both groups. An evaluation was carried out every 2-3 cycles. The primary end-points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Secondary end-points included safety and tolerability. Thirty-two patients in the pemetrexed plus cisplatin (PC) group and 28 patients in the pemetrexed plus temozolomide (PT) group were enrolled from November 2013 to October 2015. The ORR was 68.8% and 75%, in the PC and PT groups, respectively, and there was no statistically significant difference between the two groups (p=0.711). The median PFS rates of the PC and PT groups were 13.6 months and 16.9 months, respectively, and the median OS rates of the PC and PT groups were 18.9 months and 19.3 months, respectively. There were no differences in PFS and OS between the two groups. There were no grade 4 or higher side-effects in either group, but grade 3 side-effects such as leucopenia (2/32, 6.3%), nausea/vomiting (2/32, 6.3%), alopecia (1/32, 3.1%), rash (3/32, 9.4%) and renal insufficiency (1/32, 3.1%) were observed in the PC group, whereas the PT-group-only showed the following grade 3 side-effects: leucopenia (1/28, 3.6%) and nausea/vomiting (2/28, 7.1%). The data showed that the PT group achieved the same efficacy in PFS and OS as the PC group but with fewer toxicities. Therefore, high-dose pemetrexed plus temozolomide may be a better regimen for treating NSCLC with BM due to its better safety.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Encefálicas/tratamento farmacológico
Neoplasias Encefálicas/secundário
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Carcinoma Pulmonar de Células não Pequenas/patologia
[Mh] Termos MeSH secundário: Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Neoplasias Encefálicas/diagnóstico
Neoplasias Encefálicas/mortalidade
Carcinoma Pulmonar de Células não Pequenas/mortalidade
Cisplatino/administração & dosagem
Terapia Combinada
Dacarbazina/administração & dosagem
Dacarbazina/análogos & derivados
Feminino
Seres Humanos
Masculino
Meia-Idade
Metástase Neoplásica
Estadiamento de Neoplasias
Pemetrexede/administração & dosagem
Fatores de Risco
Análise de Sobrevida
Resultado do Tratamento
Carga Tumoral
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
04Q9AIZ7NO (Pemetrexed); 7GR28W0FJI (Dacarbazine); Q20Q21Q62J (Cisplatin); YF1K15M17Y (temozolomide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


  9 / 1655 MEDLINE  
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Texto completo
[PMID]:28714990
[Au] Autor:Xue Y; Martelotto L; Baslan T; Vides A; Solomon M; Mai TT; Chaudhary N; Riely GJ; Li BT; Scott K; Cechhi F; Stierner U; Chadalavada K; de Stanchina E; Schwartz S; Hembrough T; Nanjangud G; Berger MF; Nilsson J; Lowe SW; Reis-Filho JS; Rosen N; Lito P
[Ad] Endereço:Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, USA.
[Ti] Título:An approach to suppress the evolution of resistance in BRAF -mutant cancer.
[So] Source:Nat Med;23(8):929-937, 2017 Aug.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAF ) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or in combination with other ERK signaling inhibitors. Single-cell sequencing and multiplex fluorescence in situ hybridization analyses mapped the emergence of extra-chromosomal amplification in parallel evolutionary trajectories that arose in the same tumor shortly after treatment. The evolutionary selection of BRAF was determined by the fitness threshold, the barrier that subclonal populations need to overcome to regain fitness in the presence of therapy. This differed for inhibitors of ERK signaling, suggesting that sequential monotherapy is ineffective and selects for a progressively higher BRAF copy number. Concurrent targeting of the RAF, MEK and ERK kinases, however, imposed a sufficiently high fitness threshold to prevent the propagation of subclones with high-level BRAF . When administered on an intermittent schedule, this treatment inhibited tumor growth in 11/11 PDXs of lung cancer or melanoma without apparent toxicity in mice. Thus, gene amplification can be acquired and expanded through parallel evolution, enabling tumors to adapt while maintaining their intratumoral heterogeneity. Treatments that impose the highest fitness threshold will likely prevent the evolution of resistance-causing alterations and, thus, merit testing in patients.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Neoplasias Pulmonares/tratamento farmacológico
Melanoma/tratamento farmacológico
Inibidores de Proteínas Quinases/farmacologia
Neoplasias Cutâneas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adenocarcinoma/genética
Adulto
Idoso
Animais
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Bevacizumab/administração & dosagem
Carboplatina/administração & dosagem
Cisplatino/administração & dosagem
MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores
Feminino
Seres Humanos
Hibridização in Situ Fluorescente
Neoplasias Pulmonares/genética
Masculino
Melanoma/genética
Melanoma/secundário
Camundongos
Meia-Idade
Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores
Pemetrexede/administração & dosagem
Inibidores de Proteínas Quinases/uso terapêutico
Proteínas Proto-Oncogênicas B-raf/genética
Análise de Célula Única
Neoplasias Cutâneas/genética
Neoplasias Cutâneas/patologia
Ensaios Antitumorais Modelo de Xenoenxerto
Quinases raf/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); 04Q9AIZ7NO (Pemetrexed); 2S9ZZM9Q9V (Bevacizumab); BG3F62OND5 (Carboplatin); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 2.7.11.1 (raf Kinases); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4369


  10 / 1655 MEDLINE  
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[PMID]:28668866
[Au] Autor:Banna GL; Parra HJS; Castaing M; Dieci MV; Anile G; Nicolosi M; Strano S; Marletta F; Guarneri V; Conte P; Lal R
[Ad] Endereço:Division of Medical Oncology, Cannizzaro Hospital, Catania, Italy gbanna@yahoo.com.
[Ti] Título:Histology-based Combination Induction Chemotherapy for Elderly Patients with Clinical Stage III Non-small Cell Lung Cancer.
[So] Source:Anticancer Res;37(7):3723-3728, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:AIM: To explore the feasibility and activity of a histology-based induction combination chemotherapy for elderly patients with clinical stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged ≥70 years with stage IIIA and IIIB lung squamous cell carcinoma (SCC) or adenocarcinoma were treated with three cycles of carboplatin and gemcitabine or pemetrexed, respectively, followed by definitive radiotherapy or surgery. The primary endpoint was the overall response rate (ORR) following induction. RESULTS: Twenty-seven patients, with a median age of 74 years (range=70-80 years) were treated for adenocarcinoma in 14 (52%) and SCC in 13 (48%), clinical stage IIIA in eight (30%) and IIIB in 19 (70%). Grade 3 or 4 toxicity was reported for five patients (18.5%). The ORR was 46% in 12 (partial responses) out of 26 assessable patients. CONCLUSION: Histology-based induction combination chemotherapy is active and feasible in elderly patients with stage III NSCLC.
[Mh] Termos MeSH primário: Adenocarcinoma
Antineoplásicos/uso terapêutico
Carcinoma Pulmonar de Células não Pequenas
Carcinoma de Células Escamosas
Quimioterapia de Indução
Neoplasias Pulmonares
[Mh] Termos MeSH secundário: Adenocarcinoma/tratamento farmacológico
Adenocarcinoma/patologia
Adenocarcinoma/radioterapia
Adenocarcinoma/cirurgia
Idoso
Idoso de 80 Anos ou mais
Carboplatina/uso terapêutico
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Carcinoma Pulmonar de Células não Pequenas/patologia
Carcinoma Pulmonar de Células não Pequenas/radioterapia
Carcinoma Pulmonar de Células não Pequenas/cirurgia
Carcinoma de Células Escamosas/tratamento farmacológico
Carcinoma de Células Escamosas/patologia
Carcinoma de Células Escamosas/radioterapia
Carcinoma de Células Escamosas/cirurgia
Terapia Combinada
Desoxicitidina/análogos & derivados
Desoxicitidina/uso terapêutico
Feminino
Seres Humanos
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/patologia
Neoplasias Pulmonares/radioterapia
Neoplasias Pulmonares/cirurgia
Masculino
Estadiamento de Neoplasias
Pemetrexede/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 04Q9AIZ7NO (Pemetrexed); 0W860991D6 (Deoxycytidine); B76N6SBZ8R (gemcitabine); BG3F62OND5 (Carboplatin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE



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