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[PMID]:27776843
[Au] Autor:Al-Batran SE; Hofheinz RD; Pauligk C; Kopp HG; Haag GM; Luley KB; Meiler J; Homann N; Lorenzen S; Schmalenberg H; Probst S; Koenigsmann M; Egger M; Prasnikar N; Caca K; Trojan J; Martens UM; Block A; Fischbach W; Mahlberg R; Clemens M; Illerhaus G; Zirlik K; Behringer DM; Schmiegel W; Pohl M; Heike M; Ronellenfitsch U; Schuler M; Bechstein WO; Königsrainer A; Gaiser T; Schirmacher P; Hozaeel W; Reichart A; Goetze TO; Sievert M; Jäger E; Mönig S; Tannapfel A
[Ad] Endereço:Institute of Clinical Cancer Research, UCT University Cancer Center, Krankenhaus Nordwest, Frankfurt, Germany. Electronic address: albatran.salah@khnw.de.
[Ti] Título:Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial.
[So] Source:Lancet Oncol;17(12):1697-1708, 2016 Dec.
[Is] ISSN:1474-5488
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection. METHODS: In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/m on day 1, intravenous cisplatin 60 mg/m on day 1, and either fluorouracil 200 mg/m as continuous intravenous infusion or capecitabine 1250 mg/m orally (two doses of 625 mg/m per day) on days 1 to 21 (ECF/ECX group) or four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m , intravenous oxaliplatin 85 mg/m , intravenous leucovorin 200 mg/m , and fluorouracil 2600 mg/m as a 24 h infusion, all on day 1 (FLOT group). Randomisation was done centrally with an interactive web-response system based on a sequence generated with blocks (block size 2) stratified by Eastern Cooperative Oncology Group performance status, location of primary tumour, age, and nodal status. No masking was done. Central assessment of pathological regression was done according to the Becker criteria. The primary endpoint was pathological complete regression (tumour regression grade TRG1a) and was analysed in the modified intention-to-treat population, defined as all patients who were randomly assigned to treatment excluding patients who had surgery but did not provide resection specimens for central evaluation. The study (including the phase 3 part) has completed enrolment, but follow-up is ongoing and this is an interim analysis. The trial is registered with ClinicalTrials.gov, number NCT01216644. FINDINGS: Between Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10-23] of 128 patients vs eight [6%; 3-11] of 137 patients; p=0·02). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3-4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]). INTERPRETATION: Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma. FUNDING: None.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Esofágicas/tratamento farmacológico
Junção Esofagogástrica
Neoplasias Gástricas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adenocarcinoma/patologia
Adenocarcinoma/cirurgia
Adulto
Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Cisplatino/administração & dosagem
Epirubicina/administração & dosagem
Neoplasias Esofágicas/patologia
Neoplasias Esofágicas/cirurgia
Feminino
Seres Humanos
Leucovorina/administração & dosagem
Masculino
Meia-Idade
Terapia Neoadjuvante
Neoplasias Gástricas/patologia
Neoplasias Gástricas/cirurgia
Taxoides/administração & dosagem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Taxoids); 15H5577CQD (docetaxel); 3Z8479ZZ5X (Epirubicin); Q20Q21Q62J (Cisplatin); Q573I9DVLP (Leucovorin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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[PMID]:29390264
[Au] Autor:Tan J; Li X; Guo Y; Xie L; Wang J; Ma J; Jiang L
[Ad] Endereço:Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China.
[Ti] Título:Hereditary folate malabsorption with a novel mutation on SLC46A1: A case report.
[So] Source:Medicine (Baltimore);96(50):e8712, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Hereditary folate malabsorption (HFM) is characterized by folate deficiency with impaired intestinal folate absorption and impaired folate transport into the central nervous system. Its manifestations mainly include macrocytic anemia, recurrent infections, and neurological deficits. The neurological manifestations include progressive psychomotor retardation, behavioral disorders, and early-onset seizures. PATIENT CONCERNS: From early infancy, a Chinese boy had experienced macrocytic anemia, leukopenia, thrombocytopenia, recurrent pneumonia, diarrhea, and mouth ulcers. He also presented with progressive neurological symptoms. DIAGNOSIS: A novel mutation in the SLC46A1 gene was identified, and HFM was diagnosed at 18 months of age. INTERVENTIONS: After the HFM diagnosis, the boy was treated with folinic acid. LESSONS: Folinic acid supplementation is effective and may offer life-changing therapy for patients with HFM.
[Mh] Termos MeSH primário: Deficiência de Ácido Fólico/genética
Síndromes de Malabsorção/genética
Mutação
Transportador de Folato Acoplado a Próton/genética
[Mh] Termos MeSH secundário: Grupo com Ancestrais do Continente Asiático
China
Deficiência de Ácido Fólico/tratamento farmacológico
Seres Humanos
Lactente
Leucovorina/uso terapêutico
Síndromes de Malabsorção/tratamento farmacológico
Masculino
Complexo Vitamínico B/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proton-Coupled Folate Transporter); 0 (SLC46A1 protein, human); 12001-76-2 (Vitamin B Complex); Q573I9DVLP (Leucovorin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008712


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[PMID]:28448662
[Au] Autor:Al-Batran SE; Homann N; Pauligk C; Illerhaus G; Martens UM; Stoehlmacher J; Schmalenberg H; Luley KB; Prasnikar N; Egger M; Probst S; Messmann H; Moehler M; Fischbach W; Hartmann JT; Mayer F; Höffkes HG; Koenigsmann M; Arnold D; Kraus TW; Grimm K; Berkhoff S; Post S; Jäger E; Bechstein W; Ronellenfitsch U; Mönig S; Hofheinz RD
[Ad] Endereço:Institute of Clinical Cancer Research, Krankenhaus Nordwest, Universitären University Cancer Center, Frankfurt, Germany.
[Ti] Título:Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial.
[So] Source:JAMA Oncol;3(9):1237-1244, 2017 Sep 01.
[Is] ISSN:2374-2445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. Objective: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. Design, Setting, and Participants: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Interventions: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. Main Outcomes and Measures: The primary end point was overall survival. Results: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Conclusions and Relevance: Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. Trial Registration: clinicaltrials.gov identifier: NCT00849615.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Junção Esofagogástrica
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Peritoneais/tratamento farmacológico
Neoplasias Gástricas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adenocarcinoma/secundário
Adenocarcinoma/cirurgia
Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Quimioterapia Adjuvante
Fluoruracila/administração & dosagem
Gastrectomia
Seres Humanos
Leucovorina/administração & dosagem
Neoplasias Hepáticas/secundário
Neoplasias Hepáticas/cirurgia
Neoplasias Pulmonares/secundário
Neoplasias Pulmonares/cirurgia
Metástase Linfática
Metastasectomia
Meia-Idade
Terapia Neoadjuvante
Estadiamento de Neoplasias
Compostos Organoplatínicos/administração & dosagem
Neoplasias Peritoneais/secundário
Neoplasias Peritoneais/cirurgia
Estudos Prospectivos
Neoplasias Gástricas/patologia
Neoplasias Gástricas/cirurgia
Taxa de Sobrevida
Taxoides/administração & dosagem
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Organoplatinum Compounds); 0 (Taxoids); 04ZR38536J (oxaliplatin); 15H5577CQD (docetaxel); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jamaoncol.2017.0515


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[PMID]:29311468
[Au] Autor:Shida T; Endo Y; Shiraishi T; Yoshioka T; Suzuki K; Kobayashi Y; Ono Y; Ito T; Inoue T
[Ad] Endereço:Division of Pharmacy, Yamagata University Hospital.
[Ti] Título:[Economic Evaluation of mFOLFOX6-based First-line Regimens for Unresectable Advanced or Recurrent Colorectal Cancer Using Clinical Decision Analysis].
[So] Source:Yakugaku Zasshi;138(1):83-90, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:We evaluated four representative chemotherapy regimens for unresectable advanced or recurrent KRAS-wild type colorectal cancer: mFOLFOX6, mFOLFOX6+bevacizumab (Bmab), cetuximab (Cmab), or panitumumab (Pmab). We employed a decision analysis method in combination with clinical and economic evidence. The health outcomes of the regimens were analyzed on the basis of overall and progression-free survival. The data were drawn from the literature on randomized controlled clinical trials of the above-mentioned drugs. The total costs of the regimens were calculated on the basis of direct costs obtained from the medical records of patients diagnosed with unresectable advanced or recurrent colorectal cancer at Yamagata University Hospital and Yamagata Prefecture Central Hospital. Cost effectiveness was analyzed using a Markov chain Monte Carlo (MCMC) method. The study was designed from the viewpoint of public medical care. The MCMC analysis revealed that expected life months and expected cost were 20 months/3,527,119 yen for mFOLFOX6, 27 months/8,270,625 yen for mFOLFOX6+Bmab, 29 months/13,174,6297 yen for mFOLFOX6+Cmab, and 6 months/12,613,445 yen for mFOLFOX6+Pmab. Incremental costs per effectiveness ratios per life month against mFOLFOX6 were 637,592 yen for mFOLFOX6+Bmab, 1,075,162 yen for mFOLFOX6+Cmab, and 587,455 yen for mFOLFOX6+Pmab. Compared to the conventional mFOLFOX6 regimen, molecular-targeted drug regimens provide better health outcomes, but the cost increases accordingly. mFOLFOX 6+Pmab is the most cost-effective regimen among those surveyed in this study.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/economia
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/economia
Análise Custo-Benefício
Técnicas de Apoio para a Decisão
Recidiva Local de Neoplasia/dietoterapia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/economia
Bevacizumab/administração & dosagem
Bevacizumab/economia
Cetuximab/administração & dosagem
Cetuximab/economia
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Feminino
Fluoruracila/economia
Seres Humanos
Leucovorina/economia
Masculino
Cadeias de Markov
Meia-Idade
Estadiamento de Neoplasias
Compostos Organoplatínicos/economia
Taxa de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Organoplatinum Compounds); 2S9ZZM9Q9V (Bevacizumab); 6A901E312A (panitumumab); PQX0D8J21J (Cetuximab); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00159


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[PMID]:29310351
[Au] Autor:Jiang Y; Fan H; Jiang Y; Song G; Wang F; Li X; Li G
[Ad] Endereço:Department of Radiation Oncology.
[Ti] Título:Efficacy and safety of FOLFIRI and biotherapy versus FOLFIRI alone for metastatic colorectal cancer patients: A meta-analysis.
[So] Source:Medicine (Baltimore);96(48):e8767, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Previous randomized controlled trials (RCTs) and meta-analyses have demonstrated the useless of FOLFIRI alone for previously treated patients with metastatic colorectal cancer (mCRC). The role of FOLFIRI regimen combined with biological therapy is unknown. The purpose of this meta-analysis is to evaluate the efficacy and safety of combining biological therapy with chemotherapy in previously treated patients with mCRC. METHODS: MEDLINE, EMBASE, Web of Science, Cochrane library, and ClinicalTrials.gov were searched. Eligible studies were RCTs that evaluated the efficacy and safety of the FOLFIRI regimen with or without biological therapy for previously treated patients with mCRC. The hazard ratio (HR) or risk ratio (RR) with 95% confidence interval was estimated. The Chi-squared and I-squared tests were used to assess the statistical heterogeneity. RESULTS: The literature search identified 7 RCTs that met the inclusion criteria for the meta-analysis, and 3680 patients with mCRC were included. The meta-analysis showed that combined therapy was associated with a significant improved progression-free survival (PFS) (HR = 0.78, 95% CI = 0.72-0.85, P < .001), overall survival (OS) (HR = 0.84, 95% CI = 0.77-0.92, P < .001), and overall response rate (ORR) (RR = 1.70, 95% CI = 1.25-2.31, P = .001). Sensitivity analysis suggested that combined therapy versus FOLFIRI alone might increase the risk of Grade 3/4 AEs. CONCLUSION: The addition of biological therapy to the FOLFIRI regimen improved the PFS, OS, and ORR compared with FOLFIRI alone for previously treated patients with mCRC. Long-term survival outcomes are warranted.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica
Camptotecina/análogos & derivados
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/patologia
[Mh] Termos MeSH secundário: Terapia Biológica
Fluoruracila
Seres Humanos
Leucovorina
Metástase Neoplásica
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180115
[Lr] Data última revisão:
180115
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008767


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[PMID]:29277822
[Au] Autor:Bruckner HW; Gurell D; Hirschfeld A
[Ad] Endereço:MZB Foundation for Cancer Research, New York, NY, U.S.A. bruckneroncology@gmail.com.
[Ti] Título:Bevacizumab Added to Moderate-dose Chemotherapy for Refractory Uterine Cancer.
[So] Source:Anticancer Res;38(1):547-552, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs. PATIENTS AND METHODS: Eligible patients (n=9) had high-grade endometrial tumors and had failed standard chemotherapy. Bev (10 mg/kg every 2 weeks) and cyclophosphamide (150-250 mg/m ), were added to a combination of gemcitabine, fluorouracil, leucovorin, irinotecan and a platinum analogue -first without and then with docetaxel- each at approximately 1/2 to 1/3 of their standard dosage. Dose modification aimed at a repeated absolute neutrophil count (ANC) of 750-1,500 µl or platelets of 125,000-75,000 µl. Safety measures included stop-go use (intermittent, as needed, brief withholding of bev with resumption when again tolerated), of bev, and both prospective and ongoing dose modification in order to protect the bowels. RESULTS: Induction treatment was free of life-threatening complications. Nine consecutive patients, 3 under second- and 6 under multi-line treatment, had 9 objective responses and 8 produced long clinical benefits, 2 of which were complete responses. Seven responses created opportunities for personalized added treatment and research. Absolute median survival was 21.5 months for the 8 patients with platinum-resistant tumors. One patient was unable to tolerate a first standard adjuvant dose of paclitaxel. After rapid peritoneal progression of disease, treatment has produced 52+ months of unmaintained complete remission. CONCLUSION: Bev, in the combination that was used in this study, meets response, survival, and toxicity criteria for further testing against second- or multi-line chemotherapy-resistant tumors and also when a standard treatment is not safe.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Bevacizumab/uso terapêutico
Neoplasias dos Ductos Biliares/tratamento farmacológico
Colangiocarcinoma/tratamento farmacológico
Neoplasias do Endométrio/tratamento farmacológico
Neoplasias Ovarianas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adenocarcinoma/tratamento farmacológico
Camptotecina/análogos & derivados
Camptotecina/uso terapêutico
Cisplatino/uso terapêutico
Desoxicitidina/análogos & derivados
Desoxicitidina/uso terapêutico
Feminino
Fluoruracila/uso terapêutico
Seres Humanos
Quimioterapia de Indução/métodos
Leucovorina/uso terapêutico
Meia-Idade
Estudos Retrospectivos
Taxoides/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); 0 (Taxoids); 0W860991D6 (Deoxycytidine); 15H5577CQD (docetaxel); 2S9ZZM9Q9V (Bevacizumab); 7673326042 (irinotecan); B76N6SBZ8R (gemcitabine); Q20Q21Q62J (Cisplatin); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


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[PMID]:29277814
[Au] Autor:Miyamoto Y; Oki E; Emi Y; Tokunaga S; Shimokawa M; Ogata Y; Akagi Y; Sakamoto Y; Tanaka T; Saeki H; Maehara Y; Baba H
[Ad] Endereço:Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
[Ti] Título:Low Visceral Fat Content Is a Negative Predictive Marker for Bevacizumab in Metastatic Colorectal Cancer.
[So] Source:Anticancer Res;38(1):491-499, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:AIM: This study aimed to clarify the predictive impact of visceral fat on response to bevacizumab in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Pretreatment computed tomography was used to measure visceral fat area (VFA) and patients with mCRC receiving first-line chemotherapy with/without bevacizumab were divided by median VFA value into two groups: high VFA and low VFA. RESULTS: In the bevacizumab-treated group, patients with low VFA had significantly shorter overall survival (OS) than patients with high VFA in univariate (median=21.1 vs. 38.9 months; hazard ratio=1.70, 95% confidence interval=1.06-2.70, p=0.03) and multivariate analysis (hazard ratio=1.85, 95% confidence interval=1.15-3.03, p=0.01). No significant differences were seen in OS between groups treated with chemotherapy alone. The VFA had a marginally significant modifying effect on the relationship between bevacizumab and OS (p for interaction=0.07). CONCLUSION: Our findings provide the first evidence that a low VFA might be a negative predictive marker for response to bevacizumab in patients with mCRC.
[Mh] Termos MeSH primário: Inibidores da Angiogênese/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Bevacizumab/uso terapêutico
Camptotecina/análogos & derivados
Neoplasias Colorretais/tratamento farmacológico
Gordura Intra-Abdominal/fisiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Biomarcadores Tumorais/fisiologia
Camptotecina/uso terapêutico
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Feminino
Fluoruracila/uso terapêutico
Seres Humanos
Leucovorina/uso terapêutico
Masculino
Meia-Idade
Obesidade/patologia
Compostos Organoplatínicos/uso terapêutico
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Biomarkers, Tumor); 0 (Organoplatinum Compounds); 2S9ZZM9Q9V (Bevacizumab); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


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[PMID]:28463756
[Au] Autor:Stintzing S; Miller-Phillips L; Modest DP; Fischer von Weikersthal L; Decker T; Kiani A; Vehling-Kaiser U; Al-Batran SE; Heintges T; Kahl C; Seipelt G; Kullmann F; Stauch M; Scheithauer W; Held S; Moehler M; Jagenburg A; Kirchner T; Jung A; Heinemann V; FIRE-3 Investigators
[Ad] Endereço:Department of Hematology and Oncology, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. Electronic address: sebastian.stintzing@med.uni-muenchen.de.
[Ti] Título:Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-0306) study.
[So] Source:Eur J Cancer;79:50-60, 2017 07.
[Is] ISSN:1879-0852
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. METHODS: Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations. Survival analysis was done using Kaplan-Meier estimation and differences were expressed using the log-rank test. Overall response rate (ORR) was compared using Fisher's exact test. Data from a central independent radiological response evaluation were used to calculate early tumour shrinkage (ETS) and depth of response (DpR). RESULTS: Overall, 188 patients with RAS-mutant tumours and 48 with BRAF-mutant tumours were identified. In BRAF-mutant patients, ORR was numerically higher in the cetuximab versus the bevacizumab arm (52% versus 40%), while comparable results were achieved for progression-free survival (PFS; hazard ratio [HR] = 0.84, p = 0.56) and overall survival (OS; HR 0.79, p = 0.45). RAS mutation was associated with a trend towards lower ORR (37% versus 50.5%, p = 0.11) and shorter PFS (7.4 versus 9.7 months; HR 1.25; p = 0.14) in patients receiving FOLFIRI plus cetuximab versus bevacizumab, but OS was comparable (19.1 versus 20.1 months; HR 1.05; p = 0.73), respectively. ETS identified subgroups sensitive to cetuximab-based treatment in both BRAF- (9/17) and RAS-mutant (18/48) patients and was associated with significantly longer OS. DpR was comparable between both treatment arms in RAS- and BRAF-mutant patients, respectively. CONCLUSIONS: In BRAF- and RAS-mutant patients, cetuximab- and bevacizumab-based treatment had comparable survival times. ETS represents an early parameter associated with the benefit from anti-EGFR, while this was not the case with vascular endothelial growth factor A blockade.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Colorretais/genética
Mutação/genética
Proteínas Proto-Oncogênicas B-raf/genética
Proteínas Proto-Oncogênicas p21(ras)/genética
[Mh] Termos MeSH secundário: Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Bevacizumab/administração & dosagem
Camptotecina/administração & dosagem
Camptotecina/análogos & derivados
Cetuximab/administração & dosagem
Neoplasias Colorretais/tratamento farmacológico
Éxons/genética
Feminino
Fluoruracila/administração & dosagem
Seres Humanos
Leucovorina/administração & dosagem
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/secundário
Masculino
Meia-Idade
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (KRAS protein, human); 2S9ZZM9Q9V (Bevacizumab); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)); PQX0D8J21J (Cetuximab); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171230
[Lr] Data última revisão:
171230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28456090
[Au] Autor:Pernot S; Badoual C; Terme M; Castan F; Cazes A; Bouche O; Bennouna J; Francois E; Ghiringhelli F; De La Fouchardiere C; Samalin E; Bachet JB; Borg C; Ducreux M; Marcheteau E; Stanbury T; Gourgou S; Malka D; Taieb J
[Ad] Endereço:INSERM U970 - PARCC (Paris Cardiovascular Research Center), Paris Descartes University, Sorbonne Paris Cité, Paris, France; Hôpital Européen Georges-Pompidou, APHP, Department of GI Oncology, Paris Descartes University, Sorbonne Paris Cité, Paris, France.
[Ti] Título:Dynamic evaluation of circulating tumour cells in patients with advanced gastric and oesogastric junction adenocarcinoma: Prognostic value and early assessment of therapeutic effects.
[So] Source:Eur J Cancer;79:15-22, 2017 07.
[Is] ISSN:1879-0852
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The identification of dynamic biomarkers in advanced gastric and oesogastric junction adenocarcinoma (GOA) could help to tailor strategies for each patient. Enumeration of circulating tumour cells (CTCs) is approved by the US Food and Drug Administration in breast, colon and prostate cancer but is not in advanced GOA. Our study aims to establish the optimal threshold and the clinical significance of CTC count in advanced GOA before and during treatment. METHODS: One hundred six patients with untreated advanced GOA were included in the ancillary study of the PRODIGE 17-ACCORD 20 trial. CTCs were detected in the peripheral blood using the CellSearch system on day 0 (D0) and day 28 (D28). The prognostic value of CTCs at D0 and D28 was analysed by testing several thresholds. RESULTS: At baseline, median CTC count was 1 (range, 0-415). While CTCs ≥1, 2 or 3 at D0 were all significantly associated with worse overall survival (OS) and progression-free survival (PFS), CTCs ≥2 were the optimal threshold, on D0 or D28. CTCs ≥2 at D28 were also predictive of disease control. Taking into account both D0 and D28 CTC count defined 3 groups (low/low, high/low and low-high/high) with significantly different PFS (p = 0.0002) and OS (p = 0.003). CONCLUSION: Quantification of CTCs at baseline and during treatment may be a useful prognostic tool in advanced GOA, as it is associated with worse PFS and OS. A threshold ≥2 CTCs seems to have the best discriminant value. Change in CTC count between baseline and D28 could help to tailor treatment to each individual patient.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Esofágicas/patologia
Junção Esofagogástrica/patologia
Células Neoplásicas Circulantes/patologia
Neoplasias Gástricas/patologia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais Humanizados/administração & dosagem
Contagem de Células
Progressão da Doença
Intervalo Livre de Doença
Neoplasias Esofágicas/tratamento farmacológico
Feminino
Fluoruracila/administração & dosagem
Seres Humanos
Estimativa de Kaplan-Meier
Leucovorina/administração & dosagem
Masculino
Compostos Organoplatínicos/administração & dosagem
Prognóstico
Neoplasias Gástricas/tratamento farmacológico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Organoplatinum Compounds); 04ZR38536J (oxaliplatin); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171230
[Lr] Data última revisão:
171230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28742687
[Au] Autor:Limani P; Linecker M; Schneider MA; Kron P; Tschuor C; Kachaylo E; Ungethuem U; Nicolau C; Lehn JM; Graf R; Humar B; Clavien PA
[Ad] Endereço:*Department of Surgery and Transplantation, Swiss Hepato-pancreato-biliary (HPB) and Transplantation Laboratory, University Hospital Zurich, Zurich, Switzerland †Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA ‡Institute of Supramolecular Science and Engineering, University of Strasbourg, Strasbourg, France.
[Ti] Título:The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice.
[So] Source:Ann Surg;266(5):746-753, 2017 11.
[Is] ISSN:1528-1140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To test the effects of enhanced intracellular oxygen contents on the metastatic potential of colon cancer. BACKGROUND: Colorectal cancer is the commonest gastrointestinal carcinoma. Distant metastases occur in half of patients and are responsible for most cancer-related deaths. Tumor hypoxia is central to the pathogenesis of metastases. Myo-Inositoltrispyrophosphate (ITPP), a nontoxic, antihypoxic compound, has recently shown significant benefits in experimental cancer, particularly when combined with standard chemotherapy. Whether ITPP protects from distant metastases in primary colon cancer is unknown. METHODS: ITPP alone or combined with FOLFOX was tested in a mouse model with cecal implantation of green fluorescent protein-labeled syngeneic colorectal cancer cells. Tumor development was monitored through longitudinal magnetic resonance imaging-based morphometric analysis and survival. Established serum markers of tumor spread were measured serially and circulating tumor cells were detected via fluorescence measurements. RESULTS: ITPP significantly reduced the occurrence of metastases as well as other indicators of tumor aggressiveness. Less circulating tumor cells along with reduction in malignant serum markers (osteopontin, Cxcl12) were noted. The ITPP benefits also affected the primary cancer site. Importantly, animals treated with ITPP had a significant survival benefit compared with respective controls, while a combination of FOLFOX with ITPP conferred the maximum benefits, including dramatic improvements in survival (mean 86 vs 188 d). CONCLUSIONS: Restoring oxygen in metastatic colon cancer through ITPP inhibits tumor spread and markedly improves animal survival; an effect that is enhanced through the application of subsequent chemotherapy. These promising novel findings call for a clinical trial on ITPP in patients with colorectal cancer, which is under way.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias do Colo/tratamento farmacológico
Neoplasias do Colo/patologia
Fosfatos de Inositol/uso terapêutico
Neoplasias Hepáticas/prevenção & controle
Neoplasias Hepáticas/secundário
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Biomarcadores Tumorais/sangue
Neoplasias do Colo/sangue
Neoplasias do Colo/mortalidade
Ensaio de Imunoadsorção Enzimática
Fluoruracila/uso terapêutico
Imuno-Histoquímica
Fosfatos de Inositol/farmacologia
Leucovorina/uso terapêutico
Neoplasias Hepáticas/sangue
Camundongos
Camundongos Endogâmicos C57BL
Células Neoplásicas Circulantes/efeitos dos fármacos
Compostos Organoplatínicos/uso terapêutico
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Inositol Phosphates); 0 (Organoplatinum Compounds); 0 (inositol trispyrophosphate); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171214
[Lr] Data última revisão:
171214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1097/SLA.0000000000002431



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