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1.
Medicine (Baltimore) ; 98(40): e17164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577707

RESUMO

INTRODUCTION: The PD-1 inhibitors have shown good response in the treatment for many types of malignant tumors, but as monotherapy for advanced esophageal squamous carcinoma, the objective response rate is low. Here we report a case of the patient with advanced esophageal squamous cell carcinoma (ESCC) showing a completely response to nivolumab combined with a small molecule multi-target tyrosine kinase inhibitor (TKI) anlotinib. PATIENT CONCERNS: A 61-year-old male was put under a surgery as the response to the diagnosis of ESCC in March 2014. The post-operative follow-up in March 2018 suggested a recurrence based on imagological findings, and symptoms such as shortness of breath and cough were also observed in October 2018. DIAGNOSIS: The patient was diagnosed as advanced metastatic ESCC in October 2018. INTERVENTIONS: Radical resection and esophagogastrostomy under aortic arch with left thoracotomy was performed in March 2014. As a treatment against the post-surgical recurrence, 4 courses of paclitaxel combined with nedaplatin was administered in April 2018 with an outcome of PR, followed by a combined administration of Nivolumab and anlotinib in November 2018. OUTCOMES: Chest CT during a 3-month follow-up revealed the disappearance of all the metastases, and no adverse effect was observed during the treatment. CONCLUSION: The combined treatment of nivolumab and anlotinib is likely to be considered as an optional management of advanced ESCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Indóis/uso terapêutico , Nivolumabe/uso terapêutico , Quinolinas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos
2.
Anticancer Res ; 39(10): 5741-5745, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570476

RESUMO

BACKGROUND/AIM: Cardiovascular risk factors (CVRFs) predict cardiotoxicity in cancer patients but their role in late cardiac toxicity is less clear. PATIENTS AND METHODS: This was a retrospective analysis of patients treated with anthracyclines (A) and/or trastuzumab (T) and a correlation with early (≤5 years) or late (>5 years) cardiac toxicity, and baseline CVRFs and CVRFs at toxicity time. RESULTS: A total of 610 patients were included, 422 with (Group A) and 188 without (Group B) baseline CVRFs. In group A toxicity incidence was 4.7% with all events during treatment or immediately after [mean onset time 0.7 years (range=0.2-1.6)]. Events rate was 3.2% in group B with all events after five years [mean time onset 6.9 years (range=5.2-7.5)]. All group B patients who developed late cardiac toxicity presented with CVRFs at the time of toxicity not reported before. CONCLUSION: CVRFs could predict late cardiac toxicity and their control should be part of the survivorship program.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiopatias/induzido quimicamente , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
3.
N Engl J Med ; 381(17): 1632-1643, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31566309

RESUMO

BACKGROUND: Patients with metastatic colorectal cancer with the BRAF V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy. Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling. METHODS: In this open-label, phase 3 trial, we enrolled 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens. Patients were randomly assigned in a 1:1:1 ratio to receive encorafenib, binimetinib, and cetuximab (triplet-therapy group); encorafenib and cetuximab (doublet-therapy group); or the investigators' choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan) (control group). The primary end points were overall survival and objective response rate in the triplet-therapy group as compared with the control group. A secondary end point was overall survival in the doublet-therapy group as compared with the control group. We report here the results of a prespecified interim analysis. RESULTS: The median overall survival was 9.0 months in the triplet-therapy group and 5.4 months in the control group (hazard ratio for death, 0.52; 95% confidence interval [CI], 0.39 to 0.70; P<0.001). The confirmed response rate was 26% (95% CI, 18 to 35) in the triplet-therapy group and 2% (95% CI, 0 to 7) in the control group (P<0.001). The median overall survival in the doublet-therapy group was 8.4 months (hazard ratio for death vs. control, 0.60; 95% CI, 0.45 to 0.79; P<0.001). Adverse events of grade 3 or higher occurred in 58% of patients in the triplet-therapy group, in 50% in the doublet-therapy group, and in 61% in the control group. CONCLUSIONS: A combination of encorafenib, cetuximab, and binimetinib resulted in significantly longer overall survival and a higher response rate than standard therapy in patients with metastatic colorectal cancer with the BRAF V600E mutation. (Funded by Array BioPharma and others; BEACON CRC ClinicalTrials.gov number, NCT02928224; EudraCT number, 2015-005805-35.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/administração & dosagem , Carbamatos/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Progressão da Doença , Eletrocorticografia , Feminino , Humanos , Análise de Intenção de Tratamento , Irinotecano/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
4.
N Engl J Med ; 381(16): 1535-1546, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31562797

RESUMO

BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial. METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group. RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted. CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ipilimumab/administração & dosagem , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Seguimentos , Humanos , Ipilimumab/efeitos adversos , Melanoma/genética , Melanoma/mortalidade , Pessoa de Meia-Idade , Mutação , Nivolumabe/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida
5.
Zhonghua Zhong Liu Za Zhi ; 41(9): 698-702, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550861

RESUMO

Objective: To analyze the efficacy and safety of cytoreduction surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) in the early stage. Methods: The clinical data, including pathological features, recurrence and survival of 65 PMP patients in the early stage underwent CRS combined with HIPEC in Aerospace Center Hospital from January, 2011 to December, 2018 were retrospectively analyzed. Results: 65 patients with early stage PMP underwent CRS+ HIPEC. Among these patients, 25 were males and 40 were females, and the mean age was 52.5 years. The median peritoneal cancer index was 3 (0-16). The score of completeness of cytoreduction (CC) of 63 patients (96.9%) was 0, and 2 patients (3.1%) was 1. No perioperative death occurred, the incidence of surgical complications above grade 3 was 3.1%. Three patients relapsed during the follow-up period, including 1 patient with low-grade PMP, 1 patient with high-grade PMP, and 1 patient with high-grade PMP accompanied by signet ring cell. The 5-year disease-free survival rate of the whole group was 92.4%. Conclusions: PMP patients in the early stage treated by CRS combined with HIPEC can achieve benefit and safety. A close long-term follow-up is necessary.


Assuntos
Neoplasias do Apêndice/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Cancer Invest ; 37(8): 376-386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474153

RESUMO

This meta-analysis aims to evaluate the effectiveness of chemotherapy before (I-CRT) or after (CRT-C) chemoradiotherapy (CRT) for inoperable locally advanced non-small cell lung cancer (LA-NSCLC). According to the object response rate (ORR) and disease control rate (DCR), there were no differences among I-CRT, CRT, and CRT-C treatments. I-CRT did not have significant survival benefits compared with CRT alone. Similar results comparing CRT-C with CRT were observed. Furthermore, I-CRT was not associated with improved survival compared to CRT-C with respect to OS and PFS. Our meta-analysis suggests the effects of additional chemotherapy added to CRT were limited for unselected LA-NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
7.
Expert Opin Investig Drugs ; 28(10): 835-849, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31510809

RESUMO

Introduction: The incidence of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is increasing with the aging population. Prognosis and overall survival (OS) remain poor in elderly patients and in those not eligible for intensive treatment. Hypomethylating agents (HMAs) have played an important role in this group of patients but their efficacy is limited. Areas covered: This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecitabine, a second-generation DNA methylation inhibitor in development for the treatment of AML and MDS. Expert opinion: Although guadecitabine did not yield improved complete remission (CR) rates and OS compared to the control arm in patients with treatment-naïve AML who were ineligible for intensive chemotherapy, subgroup analysis in patients who received ≥4 cycles of therapy demonstrated superior outcomes in favor of guadecitabine. Given its stability, ease of administration, safety profile and prolonged exposure time, guadecitabine would be the more appropriate HMA, replacing azacitidine and decitabine, to be used combination treatment regimens in patients with myeloid malignancies.


Assuntos
Azacitidina/análogos & derivados , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Azacitidina/farmacologia , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Humanos , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/patologia , Prognóstico , Taxa de Sobrevida , Fatores de Tempo
8.
Expert Opin Investig Drugs ; 28(10): 821-826, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31526130

RESUMO

Introduction: The conventional management of most patients with metastatic urothelial carcinoma (UC) is platinum-based chemotherapy followed by immunotherapy. Erdafitinib is an option in post-platinum patients with activating mutations in fibroblast growth factor receptor (FGFR)-3 and -2. Salvage therapy with taxanes or vinflunine has demonstrated minimal efficacy. Enfortumab Vedotin (EV), a monoclonal antibody-drug conjugate (ADC) targeting nectin-4 is under investigation in patients with advanced UC. Areas covered: This review describes the epidemiology and unmet needs of patients with metastatic UC and is focused specifically on heavily treated patients. We explore the rationale for targeting nectin 4 and the clinical development of EV; efficacy and safety data from the completed phase I and II studies are examined. Ongoing trials to definitively assess clinical outcomes in comparison to current therapy and trials exploring EV in combination are also highlighted. Expert opinion: There is an unmet need for new therapies in most patients with advanced UC and who progress after platinum and immunotherapy. EV has shown promising efficacy and safety in this population in phase 1 and 2 trials including those with poor prognostic factors such as liver metastases. Ongoing trials exploring this agent in combination will continue to advance the treatment of UC.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células de Transição/imunologia , Moléculas de Adesão Celular/imunologia , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Imunoconjugados/farmacologia , Imunoterapia/métodos , Metástase Neoplásica , Oligopeptídeos/imunologia , Prognóstico , Neoplasias Urológicas/imunologia
9.
Anticancer Res ; 39(9): 4597-4602, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519556

RESUMO

Our previous review of the literature assessed the existing knowledge (until 2000) about the possible link between angiotensin-converting enzyme inhibitors (ACEIs) and factors influencing the development of malignancies. We reviewed the literature for reports of statistical associations (or lack thereof) between ACEi treatment and incidence of specific cancers (e.g. breast, gastrointestinal, and skin). We concluded then that results from the epidemiological studies are conflicting, even taking the different methodology and endpoints into consideration, and thus inconclusive. Further investigation is needed beyond the observation period of most of these studies, and additional experimental studies are needed also to study the mechanisms by which agents blocking the renin-angiotensin system may obtain their inhibitory effect on tumor growth and metastasis. The present review elaborates further with more recent evidence from numerous human clinical studies from the past two decades (including large epidemiological studies, and long-term prospective and retrospective studies) on a protective association between ACEi treatment and the prognosis of patients with specific cancer types, malignancy characteristics or stage. Moreover, treatment with ACEI/angiotensin receptor blockers represents an adjuvant therapy with synergistic effects to chemotherapy and may improve patient outcomes (i.e. progression-free survival, and prolonged overall survival) in different types of cancers.


Assuntos
Neoplasias/metabolismo , Neoplasias/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Progressão da Doença , Humanos , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/etiologia , Prognóstico , Resultado do Tratamento
10.
Anticancer Res ; 39(9): 4619-4625, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519559

RESUMO

Cancer patients are at risk for both venous and arterial thrombotic events. Accumulating evidence suggests a link between cancer and arterial thrombosis events. The pathophysiology of arterial thrombosis in cancer is complex and multifactorial. The risk of arterial thrombosis in cancer patients relies on individual risk factors, on cancer-related hypercoagulability, on anticancer drugs and radiotherapy often via a common underlying mechanism of endothelial dysfunction. This review describes the mechanisms involved in the development of arterial thrombotic events and their clinical manifestations. Furthermore, it provides an overview on therapeutic agents associated with arterial thrombosis.


Assuntos
Artérias/patologia , Neoplasias/complicações , Trombose/etiologia , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Humanos , Neoplasias/epidemiologia , Neoplasias/patologia , Neoplasias/terapia , Neovascularização Patológica , Radioterapia/efeitos adversos , Radioterapia/métodos , Avaliação de Sintomas , Trombose/diagnóstico , Trombose/epidemiologia
11.
Anticancer Res ; 39(9): 4667-4671, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519565

RESUMO

BACKGROUND/AIM: Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. MATERIALS AND METHODS: Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. RESULTS: The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. CONCLUSION: The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Modelos Animais de Doenças , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Anticancer Res ; 39(9): 4911-4916, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519595

RESUMO

BACKGROUND/AIM: The occurrence of somatic transformation in germ cell tumour (GCT) is rare, with increased incidence in teratomatous tumours. The aim of this study was to understand the clinical outcomes of patients with metastatic GCT with somatic transformation. MATERIALS AND METHODS: A retrospective study was conducted in two tertiary cancer centres in London. Between 1998 and 2016, 30 cases of somatic transformation in GCT treated at the Mount Vernon Cancer Centre and St. Bartholomew's Hospital were identified. The median age at diagnosis was 34 years (range=18-56 years). The histological diagnosis at transformation was rhabdomyosarcoma, sarcomatoid yolk sac, sarcoma (non-specified), clear cell carcinoma, adenocarcinoma and primitive neuro ectodermal tumour (PNET). RESULTS: The 5-year survival rate of all patients was 47%, and that of patients with testicular primary (n=26 patients) was 37%. CONCLUSION: Somatic transformation component in testicular GCTs is generally considered to be an adverse prognostic factor, however, a reasonable 5-year overall survival rate (87.5%) was observed in patients who present with this at first diagnosis.


Assuntos
Transformação Celular Neoplásica/genética , Mutação , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/genética , Neoplasias Testiculares/secundário , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Suscetibilidade a Doenças , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Retratamento , Análise de Sobrevida , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Resultado do Tratamento , Adulto Jovem
13.
Anticancer Res ; 39(9): 4925-4931, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519597

RESUMO

BACKGROUND/AIM: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy where antioxidant enzyme peroxiredoxin 6 (Prx6) has previously been associated with adverse outcomes. Its systemic effects in DLBCL are unknown. MATERIALS AND METHODS: This study included 53 patients with DLBCL, five patients with primary central nervous system lymphoma (PCNSL) and 20 healthy controls. The expression of Prx6 was evaluated immunohistochemically in DLBCL tissue samples and compared to its expression in blood serum. RESULTS: Prx6 expression was the highest in healthy controls, followed by DLBCL patients and PCNSL patients. Febrile neutropenic infection after the first treatment course was associated with low pre-treatment Prx6 serum levels (<14 ng/ml) (p=0.025, OR=8.615, 95% confidence interval=1.032-71.933). Serum levels of Prx6 recovered after treatment (p=0.006). CONCLUSION: Patients with low Prx6 levels might be more prone to treatment-related adverse effects through elevated levels of oxidative stress.


Assuntos
Infecção/etiologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/complicações , Neutropenia/complicações , Neutropenia/etiologia , Peroxirredoxina VI/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medição de Risco , Fatores de Risco
14.
Anticancer Res ; 39(9): 4987-4993, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519605

RESUMO

BACKGROUND/AIM: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. PATIENTS AND METHODS: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. RESULTS: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. CONCLUSION: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Docetaxel/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
15.
Anticancer Res ; 39(9): 5003-5007, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519607

RESUMO

Incorporating bortezomib and/or lenalidomide in the management of plasmablastic lymphoma is an attractive option due to the reported high response rates. However, concerns about overlapping toxicities can deter clinicians from incorporating these novel agents into chemotherapy. In this case report we describe a patient with plasmablastic lymphoma, who received both lenalidomide and bortezomib as part of upfront treatment for a high-risk plasmablastic lymphoma. After completing intensive chemotherapy, the patient was transitioned to a regimen of daily lenalidomide and biweekly bortezomib to decrease the chance of relapse. This maintenance phase was given for 6 months and was well tolerated. Despite having multiple adverse risk factors, the patient remains in remission, 18 months following diagnosis.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Linfoma Plasmablástico/tratamento farmacológico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Bortezomib/administração & dosagem , Gerenciamento Clínico , Feminino , Humanos , Quimioterapia de Indução , Imagem por Ressonância Magnética , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Linfoma Plasmablástico/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
16.
Anticancer Res ; 39(9): 5089-5096, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519620

RESUMO

BACKGROUND/AIM: We evaluated the clinical impact of FOLFOXIRI regimen aiming for conversion surgery in patients with unresectable multiple colorectal liver metastasis (CRLM). PATIENTS AND METHODS: A total of 42 patients with unresectable multiple CRLM who received chemotherapy with molecular agents were included in the analysis. The clinical results of FOLFOXIRI with other regimens were compared. RESULTS: The total conversion rate of 42 unresectable CRLM was 48.1%, and conversion cases had a better prognosis. Clinicopathological characteristics of conversion cases were more frequent in FOLFOXIRI induction, liver limited disease and maximum diameter × number (MDN) over 70. FOLFOXIRI achieved a higher conversion rate compared to other regimens (72.2% vs. 37.5%, p=0.0334), and significantly reduced the medication period until conversion surgery (median 5.8 courses) with a higher tumour necrotic rate. Consequently, the overall survival of conversion cases with FOLFOXIRI was better than that with other regimens (p=0.0055). CONCLUSION: FOLFOXIRI plus molecular agents might provide a higher probability of conversion surgery with a prognostic benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Neoplasias Colorretais/diagnóstico , Terapia Combinada , Conversão para Cirurgia Aberta , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Resultado do Tratamento , Carga Tumoral
17.
Cancer Treat Rev ; 79: 101887, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491661

RESUMO

Small cell lung cancer (SCLC) was defined as a "recalcitrant cancer" because of its dismal prognosis and lack of outcome improvements in the last 30 years. Immunotherapy with checkpoint inhibitors revolutionized treatment in many cancer types and results from the IMpower133 study, a double-blind placebo-controlled phase III trial, showed overall survival benefit for atezolizumab when added to standard platinum-etoposide chemotherapy in first-line SCLC setting for the first time since years. Trials with other checkpoint inhibitors, e.g. pembrolizumab, durvalumab, nivolumab and ipilimumab, are ongoing in various settings, but, to date, there are no defined factors to identify patients who are more likely to benefit from such treatments. This review summarizes results of immunotherapy trials in SCLC for first-line, maintenance and further-line therapies for single-agents and combinations with checkpoint inhibitors. Predictive factors from these trials are reviewed in order to identify their clinical value, with particular emphasis on PD-L1 expression on both tumor cells and in stroma, especially in pembrolizumab-treated patients, and tumor mutational burden, for patients treated with the ipilimumab and nivolumab combination.


Assuntos
Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
18.
Rinsho Ketsueki ; 60(8): 929-931, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484892

RESUMO

A 51-year-old man was diagnosed with stage IV mantle cell lymphoma based on terminal ileum biopsy and treated with the R-CHOP regimen. Abdominal CT to assess continuous fever after three courses of R-CHOP revealed three low-density areas in the liver. PCR of the fluid obtained by percutaneous drainage revealed Entamoeba histolytica positivity, although the cultures were negative. Metronidazole treatment achieved cure. The patient was not a homosexual but had an 8-month stay in Lesotho 21 years ago, leading to the possibility that E. histolytica infection at the time continued as an asymptomatic colonization until the initiation of corticosteroid-containing chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Entamoeba histolytica , Abscesso Hepático Amebiano , Linfoma de Célula do Manto , Anticorpos Monoclonais Murinos/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Humanos , Abscesso Hepático Amebiano/induzido quimicamente , Linfoma de Célula do Manto/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Vincristina/efeitos adversos
19.
Anticancer Res ; 39(9): 5219-5223, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519636

RESUMO

AIM: This study evaluated the prognostic value of soluble mesothelin-related protein (SMRP) levels in pleural effusions (PE) from patients with pleural mesothelioma (MPM). PATIENTS AND METHODS: SMRP level in PE was tested using an enzyme-linked immunosorbent assay (ELISA) in 109 patients with MPM at diagnosis before any treatment. The Kaplan-Meier method and the Cox regression were applied to compare overall survival probabilities across tertile categories of SMRP level. RESULTS: No significant differences in Kaplan-Meier overall survival probabilities among the SMRP categories were found. A statistically non-significant trend for increased death rate ratio (RR) was computed (p=0.327) when the higher (>46.5 nM, RR=1.38) and intermediate (8.5-46.5 nM, RR=1.18) SMRP categories were compared to the lower category (<8.5 nM, RR=1.00). Cox regression modelling including a restricted cubic spline showed a moderately rising non-linear trend in death rate. CONCLUSION: The SMRP level in PE does not appear to have prognostic significance and its detection is not recommended in routine clinical management of patients with MPM.


Assuntos
Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Mesotelioma/complicações , Mesotelioma/mortalidade , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurais/complicações , Neoplasias Pleurais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/terapia , Pessoa de Meia-Idade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Prognóstico , Curva ROC , Resultado do Tratamento
20.
Gan To Kagaku Ryoho ; 46(9): 1437-1439, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530785

RESUMO

A 63-year-old man was diagnosed with gastric cancer. Distal gastrectomywas performed in November 2011. The pathologic finding was pT3N2M0, Stage ⅢA. S-1 was administered as adjuvant chemotherapy. However, in August 2012, computed tomographyrevealed a tumor measuring 3 cm in size in the dorsal pancreas. Based on endoscopic ultrasound-guided fine- needle aspiration, he was diagnosed with lymph node recurrence of gastric cancer. Injection chemotherapy of CDDP/CPT-11 was initiated in November 2012. In January 2013, the patient developed fever owing to a ruptured abscess from the posterior wall in the stomach. In the 6 years since, although the patient has not undergone chemotherapy, recurrence has not been observed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino , Humanos , Irinotecano , Linfonodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
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