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[PMID]:28453695
[Au] Autor:Suenaga M; Schirripa M; Cao S; Zhang W; Yang D; Murgioni S; Rossini D; Marmorino F; Mennitto A; Ning Y; Okazaki S; Berger MD; Miyamoto Y; Gopez R; Barzi A; Yamaguchi T; Loupakis F; Lenz HJ
[Ad] Endereço:Department of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
[Ti] Título:Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.
[So] Source:Ann Oncol;28(5):1015-1022, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias Colorretais/genética
Enzimas Reparadoras do DNA/genética
Neoplasias Hepáticas/genética
Trifluridina/uso terapêutico
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/farmacologia
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Intervalo Livre de Doença
Combinação de Medicamentos
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Estudos de Associação Genética
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/mortalidade
Neoplasias Hepáticas/secundário
Masculino
Meia-Idade
Compostos de Fenilureia/farmacologia
Compostos de Fenilureia/uso terapêutico
Modelos de Riscos Proporcionais
Piridinas/farmacologia
Piridinas/uso terapêutico
Estudos Retrospectivos
Resultado do Tratamento
Trifluridina/farmacologia
Uracila/farmacologia
Uracila/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (Phenylurea Compounds); 0 (Pyridines); 0 (TAS 102); 24T2A1DOYB (regorafenib); 56HH86ZVCT (Uracil); EC 6.5.1.- (DNA Repair Enzymes); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx035


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[PMID]:28760399
[Au] Autor:Kuboki Y; Nishina T; Shinozaki E; Yamazaki K; Shitara K; Okamoto W; Kajiwara T; Matsumoto T; Tsushima T; Mochizuki N; Nomura S; Doi T; Sato A; Ohtsu A; Yoshino T
[Ad] Endereço:National Cancer Center Hospital East, Kashiwa, Japan.
[Ti] Título:TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open-label, single-arm, multicentre, phase 1/2 study.
[So] Source:Lancet Oncol;18(9):1172-1181, 2017 Sep.
[Is] ISSN:1474-5488
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In patients with heavily treated metastatic colorectal cancer, TAS-102-a combination of trifluridine and tipiracil-has shown a significant overall survival benefit compared with placebo. In preclinical models, TAS-102 plus bevacizumab has shown enhanced activity against colorectal cancer xenografts compared with that for either drug alone. In this phase 1/2 study, we assessed the activity and safety of TAS-102 plus bevacizumab. METHODS: We did this investigator-initiated, open-label, single-arm, multicentre, phase 1/2 trial of TAS-102 plus bevacizumab in four cancer centres in Japan. Eligible patients were aged 20 years or older; had histologically confirmed unresectable, metastatic colorectal adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumours with wild-type KRAS); and had no previous treatment with regorafenib. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Using a dose de-escalation design in phase 1, the recommended phase 2 dose (RP2D) was determined for TAS-102 (35 mg/m given orally twice daily on days 1-5 and 8-12 in a 28-day cycle for level 1) plus bevacizumab (5 mg/kg, administered by intravenous infusion for 30 min every 2 weeks). In phase 2, patients received the RP2D. The primary endpoint was centrally assessed progression-free survival at 16 weeks, analysed in the first 21 patients to be enrolled and treated with the RP2D who had at least one imaging assessment. This study is completed and registered with the University Hospital Medical Information Network, number UMIN000012883. FINDINGS: Between Feb 25, 2014, and July 23, 2014, we enrolled 25 patients with metastatic colorectal cancer: six patients in phase 1 and 19 patients in phase 2. The six patients who received TAS-102 at level 1 experienced no dose-limiting toxicities and this was deemed the RP2D. Nine of 21 patients who received the RP2D did not have a centrally assessed progression event; 16-week progression-free survival was 42·9% (80% CI 27·8-59·0). The most common grade 3 or worse adverse events as assessed in all 25 patients were neutropenia (18 [72%] patients), leucopenia (11 [44%]), anaemia (four [16%]), febrile neutropenia (four [16%]), and thrombocytopenia (three [12%]). Treatment-related serious adverse events were reported in three (12%) patients. No treatment-related deaths occurred. INTERPRETATION: TAS-102 plus bevacizumab has promising activity with manageable safety, suggesting that this combination might become a potential treatment option for patients with metastatic colorectal cancer in a refractory setting. FUNDING: Taiho Pharmaceutical.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Adenocarcinoma/secundário
Inibidores da Angiogênese/uso terapêutico
Bevacizumab/uso terapêutico
Neoplasias Colorretais/patologia
Trifluridina/uso terapêutico
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Adenocarcinoma/mortalidade
Adulto
Idoso
Neoplasias Colorretais/mortalidade
Intervalo Livre de Doença
Combinação de Medicamentos
Quimioterapia Combinada
Feminino
Seres Humanos
Japão
Masculino
Meia-Idade
Uracila/uso terapêutico
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Drug Combinations); 0 (TAS 102); 2S9ZZM9Q9V (Bevacizumab); 56HH86ZVCT (Uracil); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE


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[PMID]:28738235
[Au] Autor:Vogel A; Hofheinz RD; Kubicka S; Arnold D
[Ad] Endereço:Department of Gastroenterology, Hepatology and Endocrinology, Hanover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
[Ti] Título:Treatment decisions in metastatic colorectal cancer - Beyond first and second line combination therapies.
[So] Source:Cancer Treat Rev;59:54-60, 2017 Sep.
[Is] ISSN:1532-1967
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important. New options have entered the therapeutic field recently: Regorafenib is a multikinase inhibitor approved for mCRC patients who have progressed on chemotherapy (including fluoropyrimidines, irinotecan, and oxaliplatin), plus VEGF inhibitor(s) and - if RAS wild-type - an anti-EGFR inhibitor. Regorafenib significantly improved OS, compared to placebo, in two phase III trials (CORRECT and CONCUR) in mCRC patients. Trifluridine/Tipiracil, an oral fluoropyrimidine, also resulted in significantly improved OS when compared to placebo in the phase III RECOURSE trial, which was conducted in a similar patient population to CORRECT. Reintroduction of previously administered therapy is another valid and commonly used approach, especially for those regimens which were discontinued before progression, e.g. if associated with cumulative toxicities, such as peripheral neuropathy or due to treatment breaks. Re-challenge of drugs to which patients developed resistance is also feasible although evidence for this strategy is limited.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/mortalidade
[Mh] Termos MeSH secundário: Adulto
Idoso
Ensaios Clínicos Fase III como Assunto
Neoplasias Colorretais/patologia
Intervalo Livre de Doença
Feminino
Seres Humanos
Masculino
Meia-Idade
Invasividade Neoplásica/patologia
Metástase Neoplásica
Estadiamento de Neoplasias
Compostos de Fenilureia/administração & dosagem
Prognóstico
Piridinas/administração & dosagem
Medição de Risco
Análise de Sobrevida
Resultado do Tratamento
Trifluridina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Phenylurea Compounds); 0 (Pyridines); 24T2A1DOYB (regorafenib); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170725
[St] Status:MEDLINE


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[PMID]:28551618
[Au] Autor:Gong J; Chen Y; Yang L; Pillai R; Shirasawa S; Fakih M
[Ad] Endereço:Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, U.S.A.
[Ti] Título:MEK162 Enhances Antitumor Activity of 5-Fluorouracil and Trifluridine in KRAS-mutated Human Colorectal Cancer Cell Lines.
[So] Source:Anticancer Res;37(6):2831-2838, 2017 06.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Preclinical evidence demonstrates that mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway inhibition increases sensitivity to 5-fluorouracil (5-FU) in colorectal cancer (CRC) cell lines and xenografts. Here, we aimed to investigate how CRC cell sensitivity to this combination is correlated to Kirsten rat sarcoma (KRAS) and proto-oncogene B-rapidly accelerated fibrosarcoma (BRAF) mutation, that are common in CRC and often lead to resistance to chemotherapy. MATERIALS AND METHODS: Wild-type and mutant KRAS/BRAF human CRC cell lines were treated with escalating doses of 5-FU or trifluridine with MEK162 (MEK1/2 inhibitor) for 72 h. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and synergism expressed by the combination index was calculated using CalcuSyn. RESULTS: Evidence of synergistic antitumor activity was observed for the majority of human CRC cell lines treated with MEK162 plus 5-FU (4/6) or trifluridine (7/9). Synergism was greater in KRAS- or BRAF-mutant cell lines compared to wild-type KRAS/BRAF CRC cell lines. CONCLUSION: The combination of MEK inhibition and trifluridine is worthwhile advancing in clinical development, particularly for treatment-refractory KRAS- or BRAF-mutated metastatic CRC.
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/farmacologia
Benzimidazóis/farmacologia
Fluoruracila/farmacologia
Inibidores de Proteínas Quinases/farmacologia
Trifluridina/farmacologia
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Neoplasias Colorretais/genética
Seres Humanos
MAP Quinase Quinase 1/antagonistas & inibidores
MAP Quinase Quinase 2/antagonistas & inibidores
Mutação
Proteínas Proto-Oncogênicas p21(ras)/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Benzimidazoles); 0 (KRAS protein, human); 0 (MEK162); 0 (Protein Kinase Inhibitors); EC 2.7.12.2 (MAP Kinase Kinase 1); EC 2.7.12.2 (MAP Kinase Kinase 2); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)); RMW9V5RW38 (Trifluridine); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170529
[St] Status:MEDLINE


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[PMID]:28315543
[Au] Autor:White T; Larson H; Minnella A; Hochster HS
[Ad] Endereço:Yale University.
[Ti] Título:Metastatic Colorectal Cancer: Management With Trifluridine/Tipiracil
.
[So] Source:Clin J Oncol Nurs;21(2):E30-E37, 2017 Apr 01.
[Is] ISSN:1538-067X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Treatment-related adverse events (AEs) are common in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy. These AEs may affect patient adherence, particularly with completely oral regimens, such as trifluridine/tipiracil (TAS-102, Lonsurf®), an antimetabolite agent for patients with mCRC refractory or intolerant to standard therapies.
. OBJECTIVES: This article reviews strategies for promoting adherence and educating patients and caregivers about oral therapy with trifluridine/tipiracil. 
. METHODS: Recommended strategies for managing AEs are reviewed, with a focus on the most common AEs reported in patients with mCRC receiving trifluridine/tipiracil in clinical trials.
. FINDINGS: Oncology nurses play an important role in educating and counseling patients regarding treatment and its potential side effects. Among patients with mCRC refractory or intolerant to standard therapies, trifluridine/tipiracil was found to have a favorable safety profile. It is associated with hematologic AEs as well as a low incidence of nausea, diarrhea, vomiting, anorexia, and fatigue.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Colorretais/tratamento farmacológico
Náusea/induzido quimicamente
Trifluridina/efeitos adversos
Vômito/induzido quimicamente
Vômito/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Oral
Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Masculino
Meia-Idade
Náusea/tratamento farmacológico
Metástase Neoplásica/tratamento farmacológico
Trifluridina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:N
[Da] Data de entrada para processamento:170319
[St] Status:MEDLINE
[do] DOI:10.1188/17.CJON.E30-E37


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[PMID]:27576095
[Au] Autor:Giampieri R; Restivo A; Pusceddu V; Del Prete M; Maccaroni E; Bittoni A; Faloppi L; Andrikou K; Bianconi M; Cabras F; Berardi R; Zorcolo L; Scintu F; Cascinu S; Scartozzi M
[Ad] Endereço:Department of Medical Oncology, University Hospital, Polytechnic University of the Marche, Ancona, Italy.
[Ti] Título:The Role of Aspirin as Antitumoral Agent for Heavily Pretreated Patients With Metastatic Colorectal Cancer Receiving Capecitabine Monotherapy.
[So] Source:Clin Colorectal Cancer;16(1):38-43, 2017 Mar.
[Is] ISSN:1938-0674
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The potential clinical impact of aspirin use beyond its canonical indications is a novel matter of scientific debate. In patients with metastatic colorectal cancer failing all available options, regorafenib and TAS 102 represent the only chance of treatment. Although effective, these therapeutic options bring along a not-negligible burden in terms of economic costs and toxicity. In this setting, the indication to use aspirin in combination with chemotherapy would potentially represent a medical revolution under the economic and toxicity profile. PATIENTS AND METHODS: We assessed the role of aspirin in patients with metastatic colorectal cancer who failed all previous treatments and were receiving capecitabine as a salvage option before the introduction of regorafenib and TAS-102. RESULTS: Sixty-six patients were eligible. Twenty patients (30%) were on incidental treatment with aspirin for cardiovascular diseases. Twelve (60%) partial responses were seen in patients on treatment with aspirin, compared with 3 (6%) partial responses in the remaining patients (P = .00007). Sixteen patients on aspirin (80%) obtained disease control versus 14 (30%) patients who were not on aspirin (P = .000377). The median progression-free survival for patients receiving treatment with aspirin was 6.5 months versus 3.3 months for patients who were not on aspirin (hazard ratio, 0.48; 95% confidence interval, 0.30-0.79; P = .0042). A significantly improved overall survival was also evident in aspirin users (median overall survival, 14.7 vs. 8.7 months, respectively; hazard ratio, 0.43; 95% confidence interval, 0.26-0.72; P = .0023). CONCLUSION: Aspirin may improve the clinical outcome of heavily pre-treated patients with metastatic colorectal cancer receiving chemotherapy. Further studies are necessary before application in the clinical practice.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Aspirina/administração & dosagem
Capecitabina/administração & dosagem
Neoplasias Colorretais/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Antineoplásicos/administração & dosagem
Neoplasias Colorretais/secundário
Combinação de Medicamentos
Feminino
Seres Humanos
Masculino
Meia-Idade
Compostos de Fenilureia/administração & dosagem
Piridinas/administração & dosagem
Trifluridina/administração & dosagem
Uracila/administração & dosagem
Uracila/análogos & derivados
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (Phenylurea Compounds); 0 (Pyridines); 0 (TAS 102); 24T2A1DOYB (regorafenib); 56HH86ZVCT (Uracil); 6804DJ8Z9U (Capecitabine); R16CO5Y76E (Aspirin); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160831
[St] Status:MEDLINE


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[PMID]:27522626
[Au] Autor:Hamauchi S; Yamazaki K; Masuishi T; Kito Y; Komori A; Tsushima T; Narita Y; Todaka A; Ishihara M; Yokota T; Tanaka T; Machida N; Kadowaki S; Fukutomi A; Ura T; Onozawa Y; Ando M; Tajika M; Muro K; Yasui H; Mori K; Taniguchi H
[Ad] Endereço:Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
[Ti] Título:Neutropenia as a Predictive Factor in Metastatic Colorectal Cancer Treated With TAS-102.
[So] Source:Clin Colorectal Cancer;16(1):51-57, 2017 Mar.
[Is] ISSN:1938-0674
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common treatment-related adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The potential predictive value of neutropenia caused by cytotoxic drugs has been reported in various types of cancer. METHODS: We retrospectively analyzed 95 consecutive patients with metastatic colorectal cancer who received TAS-102 at 2 Japanese institutions between May 2014 and May 2015. To evaluate the association between efficacy and neutropenia, patients were divided into 4 categories according to the grade of neutropenia during the first cycle of TAS-102: Category A (grade 0-1), B (grade 2-4), C (grade 0-2), and D (grade 3-4). RESULTS: Patient characteristics were as follows: median age, 64 years; male, 58%; Eastern Cooperative Oncology Group performance status 0 to 1, 91%; primary site colon, 49%; KRAS exon 2 wild, 57%; and number of metastatic site ≥ 3, 55%. The disease control rate was significantly different between Category A and B (29.2% vs. 52.6%; P = .045) and between Category C and D (30.9% vs. 72.2%; P = .002). In multivariate analysis, Category D remained a significant predictive factor for progression-free survival compared with Category C (4.3 vs. 2.0 months; hazard ratio, 0.45; P = .01). CONCLUSION: Neutropenia caused by TAS-102 during the first cycle was associated with better efficacy. Neutropenia may be a surrogate marker for adequate antitumor doses of TAS-102.
[Mh] Termos MeSH primário: Antineoplásicos/efeitos adversos
Neoplasias Colorretais/tratamento farmacológico
Neutropenia/induzido quimicamente
Trifluridina/efeitos adversos
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/administração & dosagem
Neoplasias Colorretais/secundário
Combinação de Medicamentos
Feminino
Seres Humanos
Masculino
Meia-Idade
Prognóstico
Estudos Retrospectivos
Trifluridina/administração & dosagem
Uracila/administração & dosagem
Uracila/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (TAS 102); 56HH86ZVCT (Uracil); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160815
[St] Status:MEDLINE


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[PMID]:27443414
[Au] Autor:Longo-Muñoz F; Argiles G; Tabernero J; Cervantes A; Gravalos C; Pericay C; Gil-Calle S; Mizuguchi H; Carrato-Mena A; Limón ML; Garcia-Carbonero R
[Ad] Endereço:Hospital Universitario Ramón y Cajal, Servicio Oncología Médica, (Center Affiliated with the Red Tematica de Investigacion Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), Carretera de Colmenar Viejo Km 9.100, Madrid, Spain, 28034.
[Ti] Título:Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial.
[So] Source:Clin Transl Oncol;19(2):227-235, 2017 Feb.
[Is] ISSN:1699-3055
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:PURPOSE: TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48 for OS and PFS, respectively; both P < 0.001]. The current analysis evaluates efficacy and safety of TAS-102 in the RECOURSE Spanish subgroup. METHODS: Primary and key secondary endpoints were evaluated in a post hoc analysis of the RECOURSE Spanish subgroup, using univariate and multivariate analyses. Safety and tolerability were reported with descriptive statistics. RESULTS: The RECOURSE Spanish subgroup included 112 patients (mean age 61 years, 62 % male). Median OS was 6.8 months in the TAS-102 group (n = 80) versus 4.6 months in the placebo group (n = 32) [HR = 0.47; 95 % confidence interval (CI): 0.28-0.78; P = 0.0032). Median PFS was 2.0 months in the TAS-102 group and 1.7 months in the placebo group (HR = 0.47; 95 % CI: 0.30-0.74; P = 0.001). Eighty (100 %) TAS-102 versus 31 (96.9 %) placebo patients had adverse events (AEs). The most common drug-related ≥Grade 3 AE was neutropenia (40 % TAS-102 versus 0 % placebo). There was 1 (1.3 %) case of febrile neutropenia in the TAS-102 group versus none in the placebo group. CONCLUSIONS: In the RECOURSE Spanish subgroup, TAS-102 was associated with significantly improved OS and PFS versus placebo, consistent with the overall RECOURSE population. No new safety signals were identified. CLINICALTRIALS. GOV STUDY NUMBER: NCT01607957.
[Mh] Termos MeSH primário: Neoplasias Colorretais/tratamento farmacológico
Trifluridina/uso terapêutico
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antivirais/uso terapêutico
Neoplasias Colorretais/secundário
Método Duplo-Cego
Combinação de Medicamentos
Quimioterapia Combinada
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Estadiamento de Neoplasias
Cuidados Paliativos
Prognóstico
Espanha
Taxa de Sobrevida
Uracila/uso terapêutico
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Drug Combinations); 0 (TAS 102); 56HH86ZVCT (Uracil); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170410
[Lr] Data última revisão:
170410
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160723
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1007/s12094-016-1528-7


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[PMID]:28133298
[Au] Autor:Hasegawa J; Noura S; Hirota M; Matsumura T; Yasuyama A; Takata A; Koga C; Murakami M; Kameda C; Oda N; Kawabata R; Morishima H; Shimizu J; Matsunami N
[Ad] Endereço:Dept. of Surgery, Osaka Rosai Hospital.
[Ti] Título:[A Case of Metastatic Colorectal Cancer Refractory to Standard Chemotherapies Treated with TAS-102 with Bevacizumab].
[So] Source:Gan To Kagaku Ryoho;43(12):2289-2291, 2016 Nov.
[Is] ISSN:0385-0684
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:A 51-year-oldwoman with lung, liver, andd istant lymph node metastases from sigmoidcolon cancer was treatedusing TAS-102 with bevacizumab as fourth-line chemotherapy. There was a 35%decrease in the size of target lesions after the first 4 cycles of therapy, and disease control has been maintained for 9 months. The only Grade 3 or worse adverse event experiencedwas neutropenia. In patients with refractory colorectal cancer, the combination of TAS-102 with bevacizumab might be an effective andsafe treatment.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias do Colo Sigmoide/tratamento farmacológico
[Mh] Termos MeSH secundário: Bevacizumab/administração & dosagem
Terapia Combinada
Combinação de Medicamentos
Feminino
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/secundário
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/secundário
Metástase Linfática
Meia-Idade
Neoplasias do Colo Sigmoide/cirurgia
Resultado do Tratamento
Trifluridina/administração & dosagem
Uracila/administração & dosagem
Uracila/análogos & derivados
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Combinations); 0 (TAS 102); 2S9ZZM9Q9V (Bevacizumab); 56HH86ZVCT (Uracil); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170131
[St] Status:MEDLINE


  10 / 447 MEDLINE  
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[PMID]:27809894
[Au] Autor:Kamei H; Ishibashi N; Tanigawa M; Yamaguchi K; Uchida M; Akagi Y
[Ad] Endereço:Department of Surgery, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan. kamei_hideki@med.kurume-u.ac.jp.
[Ti] Título:Interstitial pneumonia in a patient treated with TAS-102 for metastatic colorectal cancer: a case report.
[So] Source:J Med Case Rep;10(1):310, 2016 Nov 03.
[Is] ISSN:1752-1947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: TAS-102, a new treatment option for patients with metastatic colorectal cancer that is refractory or intolerant to standard therapies, has been improving survival with acceptable tolerability and adverse events. Adverse hematological events associated with TAS-102 treatment were extensively profiled in the RECOURSE trial, but pulmonary toxicities associated with TAS-102 therapy are distinctly uncommon. In a recent early post-marketing phase vigilance on TAS-102 in Japan, seven cases of pulmonary disease were reported, but patient follow-up in this study was incomplete. Here, we present the first case of interstitial lung disease occurring in association with TAS-102 treatment. CASE PRESENTATION: A 57-year-old Japanese man who had previously received two standard treatments was admitted in 2014, at which time we administered TAS-102 (110 mg/day) as a third-line chemotherapy. He was safely treated with TAS-102 for the first planned cycle; however, approximately 4 days after receiving the second cycle of TAS-102, he complained of high fever and subsequent dyspnea with severe hypoxemia and went to the emergency room. A chest X-ray revealed diffuse coarse reticular shadows with ground-glass opacity on both lungs. Furthermore, a chest computed tomography scan showed thickening of the bronchovascular bundles with extensive ground-glass opacification and pleural effusions in both lung fields. In addition, a peripheral blood lymphocyte stimulation test with TAS-102 showed higher values compared with control samples. Consequently, we suspected drug-induced interstitial pneumonia, and discontinued treatment. Our patient was given an initial administration of high-dose methylprednisolone (1000 mg/day) for 3 days and oxygen. Our patient was discharged with oral prednisolone (20 mg/day) and improved symptomatically and radiologically. CONCLUSIONS: These findings suggest that interstitial pneumonia is a rare complication of TAS-102 chemotherapy, but the possibility of interstitial pneumonia should always be considered when a patient presents with a respiratory disorder while undergoing TAS-102 systemic chemotherapy. Prompt discontinuation of TAS-102 and treatment with high-dosage corticosteroids is needed to avoid exacerbating respiratory symptoms.
[Mh] Termos MeSH primário: Antineoplásicos/efeitos adversos
Neoplasias Colorretais/tratamento farmacológico
Doenças Pulmonares Intersticiais/induzido quimicamente
Trifluridina/efeitos adversos
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Neoplasias Colorretais/secundário
Combinação de Medicamentos
Seres Humanos
Japão
Masculino
Meia-Idade
Uracila/efeitos adversos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (TAS 102); 56HH86ZVCT (Uracil); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170517
[Lr] Data última revisão:
170517
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE



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