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1.
Medicine (Baltimore) ; 99(39): e22335, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991445

RESUMO

INTRODUCTION: Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency viruses -positive patients. Oral cavity is the most commonly PBL affected site. Most oral PBLs presented as asymptomatic swellings, frequently associated with ulcerations and bleeding. Most cases lacked B-symptoms, suggesting a more local involvement of the disease. No standard treatment is yet for oral PBL. Five-year survival rate recorded no more than 33.5%. PATIENT CONCERNS: A 39-year-old male presented to Dental Clinic with 1 month swelling of the oral cavity, in absence of any other symptoms or signs. He followed antibiotic therapy just on suspicion of an oral abscess and later oral surgical treatment on suspicion of bone neoplasm. DIAGNOSIS: Surgical specimen analysis highlighted a diffuse infiltrate of large-sized atypical cells with plasmablastic appearance and plasma cell phenotype. Oral cavity PBL was diagnosed. Blood tests recorded mild lymphopenia and positive human immunodeficiency viruses serology. INTERVENTIONS: Patient underwent chemotherapy including intrathecal methotrexate prophylaxis, in addition to a highly active antiretroviral therapy. OUTCOMES: At 12 months from diagnosis, patient recorded complete hematological remission. CONCLUSIONS: Oral PBL diagnosis requires a high level of suspicion and awareness both by physicians and pathologists. They should be aware of the extent of such disease which is often mistaken as oral abscess or infected tooth, thus leading to delay the most appropriate diagnostic evaluation. As PBL is an aggressive non-Hodgkin lymphoma, a delayed diagnosis might negatively impact on both treatment and survival.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Boca/patologia , Linfoma Plasmablástico/tratamento farmacológico , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Adulto , Assistência ao Convalescente , Antibacterianos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia Combinada , Edema/etiologia , Infecções por HIV/complicações , Soropositividade para HIV/sangue , HIV-1/imunologia , Humanos , Injeções Espinhais , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Plasmócitos/patologia , Linfoma Plasmablástico/diagnóstico por imagem , Resultado do Tratamento
2.
Ann Hematol ; 99(10): 2405-2416, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32813071

RESUMO

Predictive factors of response to hypomethylating agents (HMA) in elderly acute myeloid leukemia (AML) patients remain unclear in the real-life setting and no direct comparison between azacitidine (AZA) and decitabine (DEC) has been carried out. We retrospectively evaluated 110 AML patients treated with HMA (78 AZA, 32 DEC) as first-line therapy outside of clinical trials. Median age was 75 years (range 58-87). The median overall survival (OS) of the entire cohort was 8.0 months (95% CI 6.1-10), without significant differences among the subgroups: AZA 8.8 months vs DEC 6.3 months (p = 0.291). HMA treatment yielded an overall response rate (ORR) of 40% (AZA 37% vs DEC 47%, p = 0.237). A stable disease (SD) after 4 HMA cycles was not associated with a worse survival outcome compared with an early optimal response. Factors independently associated with a better OS were transfusion independence during treatment (p = 0.049), achievement of an optimal response to treatment (p < 0.001), and a baseline hemoglobin level ≥ 9.25 (p = 0.018). A bone marrow (BM) blast count ≥ 30% (p < 0.001) and a therapy-related AML (p = 0.008) remain poor survival predictors. Of the available biologic features, an adverse risk category according to the ELN classification was significantly associated with a shorter survival over the intermediate risk category (p = 0.034). Disease progression remains the primary cause of death. Infectious complications were more severe (p = 0.036) and occurred earlier (p = 0.006) in the DEC group compared with that of the AZA group. In conclusion, clinical prognostic factors associated to response and survival have been identified without significant associations concerning overall outcomes between the two HMAs.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Metilação de DNA/efeitos dos fármacos , DNA de Neoplasias/efeitos dos fármacos , Decitabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Causas de Morte , Contagem de Células , DNA de Neoplasias/química , Progressão da Doença , Intervalo Livre de Doença , Feminino , Hemoglobinas/análise , Humanos , Infecções/etiologia , Infecções/mortalidade , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
3.
Ann Hematol ; 99(10): 2367-2375, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32816079

RESUMO

This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m2) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m2/day, 5 days/week). The total radiation dose was modulated according to the patient's response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3-4 hepatic toxicity, although 75 mg/m2/day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m2/day when administered concomitantly with radiotherapy and after HD-MTX.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Irradiação Craniana , Linfoma não Hodgkin/terapia , Temozolomida/uso terapêutico , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Quimioterapia Adjuvante , Transtornos Cognitivos/induzido quimicamente , Quimioterapia de Consolidação , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Dose Máxima Tolerável , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Neoplasia Residual , Intervalo Livre de Progressão , Estudos Prospectivos , Temozolomida/efeitos adversos , Adulto Jovem
4.
Medicine (Baltimore) ; 99(31): e21432, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756152

RESUMO

INTRODUCTION: A cesarean scar pregnancy (CSP), when combined with an arteriovenous malformation (AVM), is a rare, but potentially life-threatening condition that may be associated with uncontrolled hemorrhage. Hysterectomy is indicated when conservative treatment fails. Preservation of fertility is challenging. PATIENT CONCERNS: We reported a 33-year-old woman with a CSP combined with an AVM who failed methotrexate administration as conservative treatment. DIAGNOSES: A CSP combined with an AVM was diagnosed via three-dimensional color Doppler angiogram and magnetic resonance imaging. INTERVENTIONS: Transvaginal removal of the ectopic gestation and repair of the uterine defect was performed without incident. OUTCOMES: The fertility of the patient was preserved and hysterectomy was avoided. CONCLUSION: Transvaginal fertility-sparing surgery may be successfully performed to prevent hysterectomy when conservative treatment fails in patients with a CSP combined with an AVM.


Assuntos
Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/cirurgia , Cicatriz/patologia , Preservação da Fertilidade/métodos , Adulto , Angiografia/métodos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/tratamento farmacológico , Cesárea/efeitos adversos , Cicatriz/cirurgia , Feminino , Humanos , Imageamento Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Gravidez , Gravidez Ectópica/cirurgia , Resultado do Tratamento , Ultrassonografia Doppler em Cores/métodos
5.
Anticancer Res ; 40(8): 4263-4270, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727753

RESUMO

BACKGROUND/AIM: Enzymatic variants involved in fluoropyrimidine metabolism have been associated with adverse events (AEs). We assessed the association between C677T (rs1801133) and A1298 (rs1801131) methylenetetrahydrofolate reductase (MTHFR) polymorphisms and AEs in patients with first-line fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Fifty patients with metastatic colorectal cancer were prospectively followed-up during the first 4 cycles of fluoropyrimidine-based treatment to assess AEs. Germline DNA was analyzed to determine the C677T and A1298C MTHFR polymorphisms. The associations between MTHFR polymorphisms and toxicity were examined. RESULTS: Individuals carrying at least one mutant allele of the MTHFR C677T polymorphism had increased risk to experience anemia (OR=1.69, 95% CI=1.13-2.53, p=0.005), neutropenia (OR=2.27, 95% CI=1.47-3.42, p<0.001) thrombocytopenia (OR=1.91, 95% CI=1.30-2.70, p<0.001), neuropathy (OR=1.77, 95% CI=1.16-2.70, p=0.02), diarrhea (OR=1.69, 95% CI=1.13-2.53, p=0.005), and hand-foot syndrome (OR=1.56, 95% CI=1.08-2.27, p=0.013), compared to patients carrying the wild type alleles. The presence of the mutant allele C of the MTHFR A1298C polymorphism was associated with increased risk of anemia (OR=2.75, 95% CI=1.01-7.48, p=0.02) and thrombocytopenia (OR=3.14, 95% CI=1.01-9.78, p=0.03); however, the prevalence of this allele in the sample was quite low (20%). CONCLUSION: MTHFR C677T and A1298C polymorphisms predicted toxicity in a subset of Mestizo patients with colorectal adenocarcinoma.


Assuntos
Antimetabólitos Antineoplásicos/toxicidade , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Grupos Étnicos/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Idoso , Neoplasias Colorretais/patologia , Costa Rica , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Estudos Prospectivos
6.
Medicine (Baltimore) ; 99(24): e20094, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541448

RESUMO

OBJECTIVE: To ascertain the efficacy and safety of daunorubicin combined with cytarabine comparing with idarubicin combined with cytarabine as a standard induction therapy for acute Myeloid leukemia by a meta-analysis. METHODS: The randomized controlled trials included were retrieved from PubMed, Embase, and Cochrane library. We evaluated and cross-checked the randomized clinical trials (RCTs) comparing daunorubicin combined with cytarabine (DA) and idarubicin combined with cytarabine (IA) by two reviewers independently according to Cochrane Handbook for Systematic Reviewers of Interventions. The data of meta-analysis was conducted using Review Manager 5.3 and Stata 12.0 software. RESULTS: A total of 6 studies containing 3140 patients were included. The primary outcomes were complete remission (CR), CR in one course (CR1), CR in two courses (CR2), overall survival (OS), and relapse rate. The secondary outcomes included adverse events and cytogenetic risk in subgroup analyses. IA showed a statistically significant in CR (RR = 1.05; 95%CI = 1.00-1.09, P = .03) and CR1 (RR = 1.11; 95%CI = 1.04-1.18, P = .003), but not in CR2 (RR = 0.97; 95%CI = 0.77-1.24, P = .83), and relapse rate (RR = 1.08; 95%CI = 0.98-1.43, P = .08). In high dose daunorubicin group, OS was significantly improved with IA compared to DA (HR = 0.89, 95%CI = 0.8-1.0, P = .041, I = 0). At grade 3/4 adverse events, the difference between IA and DA was not statistically significant (infection, P = .28; cardiac toxicity, P = .15; bleeding, P = .29). In the subgroup analysis, the genotypes of the IA and DA groups were not statistically significant for comparison of CR between the two groups (P = .07). CONCLUSION: This meta-analysis showed that IA had a better efficacy in the treatment of acute myeloid leukemia than DA, even with increased doses of DA. The OS of a standard dose of IA patients was longer than that of DA patients. Our research shows that anthracycline dose intensification of daunorubicin is of no clinically relevant benefit in AML patients comparing with a standard dose of IA. When it comes to adverse drug reactions, it is not a significant difference. Therefore, in clinical practice, IA should be the first choice for induction regimen in patients with acute myeloid leukemia.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Idarubicina/uso terapêutico , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Inibidores da Topoisomerase II/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Feminino , Humanos , Idarubicina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão , Segurança , Análise de Sobrevida , Inibidores da Topoisomerase II/efeitos adversos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
7.
Medicine (Baltimore) ; 99(25): e20809, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569228

RESUMO

RATIONALE: Pyrotinib is a novel dual pan-ErbB receptor tyrosine kinase inhibitor, approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, there was still limited information regarding specific effect of pyrotinib on HER2-positive MBC patients with phosphoinositol-3 kinase mutation. PATIENT CONCERNS: A 63-year-old woman accidentally discovered a left breast lesion. The breast cancer was diagnosed by biopsy of breast lesion and postoperative pathological examination in March, 2017. The patient was presented with HER2-positive (3+), invasive carcinoma of the left breast with lymph nodes and lung nodules metastasis, and the clinical stage was T4N2M1. However, the lesion continued to aggressive disease progression with the treatment of trastuzumab plus multiple chemotherapy regimens and traditional Chinese medicine. DIAGNOSES: The woman was diagnosed with invasive carcinoma of the left breast and lymph nodes and lung nodules metastasis. INTERVENTIONS: The patient received 6 cycles of pyrotinib in combination with capecitabine regularly. OUTCOMES: Progression free survival was more than 6 months, and the patient's efficacy evaluation was partial remission. LESSONS: Our clinical observations demonstrated that pyrotinib may be an effective treatment for patients with HER2-positive MBC.


Assuntos
Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Acrilamidas/administração & dosagem , Aminoquinolinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade
8.
PLoS One ; 15(6): e0234432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516350

RESUMO

The fraction retention non-inferiority hypothesis is often measured for the ratio of the effects of a new treatment to those of the control in medical research. However, the fraction retention non-inferiority test that the new treatment maintains the efficacy of control can be affected by the nuisance parameters. Herein, a heuristic procedure for testing the fraction retention non-inferiority hypothesis is proposed based on the generalized p-value (GPV) under normality assumption and heteroskedasticity. Through the simulation study, it is demonstrated that, the performance of the GPV-based method not only adequately controls the type I error rate at the nominal level but also is uniformly more powerful than the ratio test, Rothmann's and Wang's tests, the comparable extant methods. Finally, we illustrate the proposed method by employing a real example.


Assuntos
Interpretação Estatística de Dados , Desenvolvimento de Medicamentos/métodos , Modelos Estatísticos , Projetos de Pesquisa , Resultado do Tratamento , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Simulação por Computador , Estudos de Equivalência como Asunto , Humanos , Neoplasias/tratamento farmacológico
9.
Anticancer Res ; 40(5): 2813-2819, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366428

RESUMO

BACKGROUND/AIM: Methionine addiction is a general and fundamental hallmark of cancer. Methionine addiction can be targeted by methionine restriction (MR). Our laboratory has studied methionine addiction in cancer and MR for almost 50 years. The present study describes oral recombinant methioninase (o-rMETase), as a supplement, to induce MR in cancer patients. PATIENTS AND METHODS: One patient, a 67-year-old female with high-stage ovarian cancer took o-rMETase twice a day at 250 units per dose for approximately one month. A second patient, a 76-year-old male with bone-metastatic prostate cancer, took o-rMETase twice a day at 250 units per dose during three months. RESULTS: The first patient's circulating methionine levels decreased 50% within 4 hours of taking 250 units of o-rMETase. The second patient's PSA dropped approximately 70% over 3 months. During this time the patient's hemoglobin increased. CONCLUSION: o-rMETase has no side effects and is potentially efficacious. Future studies involving larger cohorts of patients with high-stage cancer are required to determine if o-rMETase, as a supplement, can increase survival and improve the quality of life.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Liases de Carbono-Enxofre/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Antígeno Prostático Específico/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Administração Oral , Idoso , Animais , Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Ósseas/patologia , Liases de Carbono-Enxofre/farmacologia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias da Próstata/patologia , Qualidade de Vida
10.
Gan To Kagaku Ryoho ; 47(4): 615-619, 2020 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-32389963

RESUMO

An 82-year-old woman presented with a dull feeling in her stomach and anemia. The gastroscopy and abdominal CT scan showed a progressive gastric tumor with multiple liver metastases, and a biopsy specimen revealed moderately differentiated tubular adenocarcinoma. A subtotal gastrectomy with D1 plus lymph node dissection was performed. The final diagnosis was as follows: H1, P0, CY0, M1, pT3, pN2, and fStageⅣ. We considered her age, and postoperative chemotherapy with of an oral anticancer drug, S-1, was initiated at a daily dose of 100 mg, with a 2-week administration and 1-week suspension schedule. The multiple liver metastases obviously reduced in size(PR)by 3 months, and the CT scan revealed complete response(CR)by 8 months after beginning S-1 administration. However, grade 2 anorexia and general malaise developed, so the S-1 administration was changed to a daily dose of 80 mg, with a 2-week administration and 2-week suspension schedule. However, an adverse event of nausea appeared again, and the patient needed a 2-month discontinuation. Therefore, S-1 administration was changed to alternate-day administration, at a daily dose of 100 mg. Subsequently, no side effects were observed, and we continued the S-1 administration for 4 years. She has maintained a complete response(CR) for 10 years, with no obvious cancer recurrence.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Hepáticas , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas , Tegafur/uso terapêutico , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Metástase Linfática , Recidiva Local de Neoplasia
11.
Gan To Kagaku Ryoho ; 47(3): 445-447, 2020 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-32381912

RESUMO

Herein, we report a case of unresectable lung cancer in which S-1 monotherapy contributed to an improvement in the patient's quality of life and to prolonged survival. A 44-year-old man with primary pulmonary adenocarcinoma(negative driver mutation and a PD-L1 tumor proportion score of 1-24%)of clinical stage ⅢA(cT4N0M0)underwent multidisciplinary treatment as follows: 1 ) weekly carboplatin and paclitaxel plus radiotherapy as induction chemoradiotherapy, 2 ) surgery that revealed that the lesion was unresectable, 3 ) cisplatin plus pemetrexed as second-line treatment, and 4 ) pembrolizumab as third-line treatment. However, the disease progressed after 19 courses of pembrolizumab, and the patient developed cachexia due to esophageal stenosis caused by tumor enlargement. He underwent percutaneous gastrostomy and was fed via a gastrostomy tube. S-1 monotherapy(2-week administration every 3 weeks)was introduced as fourth-line treatment. After 3 courses of S-1 monotherapy, the patient complained of regurgitation of stomach fluid. Computed tomography( CT)revealed that the primary tumor had decreased in size, and he developed the ability to drink water. After 6 courses of S-1, CT revealed progressive disease, so atezolizumab was administered as fifth-line treatment. However, after 2 courses, mediastinitis due to esophageal penetration into the mediastinum occurred. The patient died 28 months after the initial treatment.


Assuntos
Adenocarcinoma de Pulmão , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Pulmonares , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adulto , Combinação de Medicamentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Qualidade de Vida
12.
Medicine (Baltimore) ; 99(18): e20082, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358392

RESUMO

BACKGROUND: To systematic review the efficacy and safety of 6-thioguanine (6-TG) in the substitute of 6-mercaptopurine (6-MP) in the treatment for patients with childhood acute lymphoblastic leukemia (ALL) in the maintenance phase, and to explore its clinical application value. It provides theoretical guidance for the maintenance treatment of ALL in children from the perspective of evidence-based medicine. METHODS: By means of computer retrieval, Chinese databases were searched: Chinese Biomedical Database (CBM), China national knowledge internet (CNKI), Chongqing Weipu Database (VIP), and Wanfang Database; Foreign databases: PubMed, The Cochrane Library, Embase, and Web of Science were applied to find out randomized controlled trial (RCT) for 6-TG in childhood acute lymphoblastic leukemia. By manual retrieval, documents without electronic edition and related conference papers were retrieved. The retrieval time ranges from the beginning of the establishment of the databases to September 1st, 2019. According to the inclusion, and exclusion criteria by 3 researchers, the literature screening, data extraction, and research methodological quality evaluation were completed. RevMan 5.3 software was applied to evaluate the quality of the included literature, and Stata 12.0 software was used to conduct meta-analysis of the outcome indicators of the included literature. RESULTS: This study systematically evaluated the efficacy and safety of 6-TG in the substitute of 6-MP as a maintenance drug for childhood acute lymphoblastic leukemia. Through the key outcome indicators, this study is expected to draw a scientific, practical conclusion for 6-TG in the treatment of childhood acute lymphoblastic leukemia. This conclusion will provide evidence-based medical direction for clinical treatment. CONCLUSION: The efficacy and safety of 6-TG in the substitute of 6-MP in the maintenance treatment of childhood acute lymphoblastic leukemia will be confirmed through this study. The conclusions will be published in relevant academic journals. REGISTRATION: PROSPERO (registration number is CRD42020150466).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Tioguanina/uso terapêutico , Adolescente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Substituição de Medicamentos , Humanos , Lactente , Mercaptopurina/uso terapêutico , Metástase Neoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Projetos de Pesquisa , Tioguanina/administração & dosagem , Tioguanina/efeitos adversos
13.
Crit Rev Oncol Hematol ; 151: 102975, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32464483

RESUMO

Patients with biliary tract cancer (BTC) have a high recurrence rate after complete surgical resection. To reduce the risk of recurrence and to improve survival, several chemotherapeutic agents that have shown to be active in locally advanced and metastatic BTC have been investigated in the adjuvant setting in prospective clinical trials. Based on the results of the BILCAP phase III trial, capecitabine was adapted as the standard of care by the ASCO clinical practice guideline. Ongoing randomized controlled trials mainly compare capecitabine with gemcitabine-based chemotherapy or chemoradiotherapy. This review provides an update of adjuvant therapy in BTC based on published data of phase II and III trials and ongoing randomized controlled trials (RCTs).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/terapia , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar/patologia , Humanos , Recidiva Local de Neoplasia , Estudos Prospectivos
14.
Oncology ; 98(8): 520-527, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369814

RESUMO

In this review, human methotrexate dosing regimens, as well as their relationship to data from in vitro cell culture and in vivo animal and human studies, are discussed. Low-dose, intermediate-dose, and high-dose therapies are covered. Since in vitro and in vivo screenings of potential cancer drugs are commonplace in the development of cancer chemotherapy, comparisons of the three criteria for effectiveness are important.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Animais , Criança , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Metotrexato/química , Neoplasias/patologia
15.
Medicine (Baltimore) ; 99(15): e19850, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282749

RESUMO

RATIONALE: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a serious complication in patients treated using methotrexate. It occasionally develops in extra-nodal sites, but rarely in the central nervous system (CNS) or in 2 different sites at the same time. We present the rare case of a patient with rheumatoid arthritis who developed lymphoma in the CNS and stomach during MTX therapy. PATIENT CONCERNS: A 75-year-old Japanese man with rheumatoid arthritis who received methotrexate was admitted to our hospital because of gait ataxia and anorexia. DIAGNOSES: Imaging findings and biopsy led to a diagnosis of 2 different types of MTX-LPD in the central nervous system and stomach. INTERVENTIONS: The lesion in his stomach improved after methotrexate withdrawal, whereas the cerebellar mass required high-dose methotrexate and rituximab therapy. OUTCOMES: Complete remission has been maintained for the 2 years following the initiation of chemotherapy. LESSONS: In patients with RA who receive MTX and develop new neurological symptoms, CNS lymphoma as an MTX-LPD may be considered as a differential diagnosis.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Artrite Reumatoide/complicações , Neoplasias do Sistema Nervoso Central/patologia , Linfoma/induzido quimicamente , Metotrexato/efeitos adversos , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Diagnóstico Diferencial , Endoscopia do Sistema Digestório/métodos , Feminino , Marcha Atáxica/diagnóstico , Marcha Atáxica/etiologia , Humanos , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Imagem por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do Tratamento
16.
Medicine (Baltimore) ; 99(17): e19480, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332600

RESUMO

BACKGROUND: The digestive tract malignancies are a series of malignant tumor with high morbidity and mortality. Traditional Chinese medicine (TCM) combined with chemotherapy drugs interventions have been applied for the treatment of malignant tumors in Asian countries for dacades. This study aimed to assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for treating digestive tract malignancies. PURPOSE: To assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for digestive tract malignancies. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when conducting the meta-analysis. Randomized controlled trials (RCTs) of Kanglaite injection combined with fluorouracil-based chemotherapy in the treatment of digestive tract malignant tumors were selected and assessed for inclusion. RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) was used for meta-analysis. The objective response rate (ORR) was defined as the primary endpoint, and the disease control rate (DCR), quality of life (QoL), and toxicities were the secondary outcomes. RESULTS: 20 RCTs enrolling 1339 patients with advanced digestive tract malignancies were included. The methodological quality of most included trials was low to moderate. Compared with fluorouracil-based chemotherapy alone, Kanglaite injection plus fluorouracil-based chemotherapy can improve DCR (risk ratio (RR) = 1.18, 95% confidence interval (CI) 1.11-1.25, P < .00001), ORR (RR = 1.35, 95% CI 1.18-1.54, P < .00001), QoL (RR = 1.58, 95% CI 1.35-1.85, P < .00001), and can reduce adverse drug reactions (ADRs) such as myelosuppression (RR = 0.33, 95% CI 0.25-0.43, P < .00001), leukopenia (RR = 0.31, 95% CI 0.22-0.43, P < .00001), thrombocytopenia (RR = 0.6, 95% CI 0.38-0.49, P = .03), neutropenia (RR = 0.26, 95% CI 0.12-0.55, P = .0005), anemia (RR = 0.41, 95% CI 0.23-0.75, P = .004), gastrointestinal reaction (RR = 0.35, 95% CI 0.27-0.46, P < .00001), nausea/vomiting (RR = 0.41, 95% CI 0.28-0.61, P < .00001), diarrhea (RR = 0.34, 95% CI 0.18-0.62, P = .0004), hepatotoxicity (RR = 0.28, 95% CI 0.17-0.47, P < .00001), neurotoxicity (RR = 0.58, 95% CI 0.41-0.82, P = .002), mucositis (RR = 0.59, 95% CI 0.29-1.21, P = .15). CONCLUSION: Kanglaite injection combined with fluorouracil-based chemotherapy could remarkably improve the clinical effectiveness and reduce the adverse effects in patients with advanced malignant tumors of the digestive tract which may provide evidence to judge whether TCM is an effective and safe intervention for the digestive tract malignancies.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Digestório/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fluoruracila/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Estadiamento de Neoplasias , Razão de Chances
17.
PLoS One ; 15(4): e0231651, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294118

RESUMO

INTRODUCTION: The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. METHODS: The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. RESULTS: Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. CONCLUSION: Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.


Assuntos
Povos Indígenas/genética , Pirofosfatases/genética , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Brasil , Humanos , Mercaptopurina/farmacologia , Mercaptopurina/uso terapêutico , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pirofosfatases/metabolismo
18.
PLoS One ; 15(4): e0231656, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294127

RESUMO

It has been reported that 20% of early-stage oral squamous cell carcinoma (OSCC) patients treated with surgery alone (SA) may exhibit postoperative relapse within 2-3 years and have poor prognoses. We aimed to determine the safety of S-1 adjuvant chemotherapy and the potential differences in the disease-free survival (DFS) between patients with T2N0 (stage II) OSCC treated with S-1 adjuvant therapy (S-1) and those treated with SA. This single-center retrospective cohort study was conducted at Kumamoto University, between April 2004 and March 2012, and included 95 patients with stage II OSCC. The overall cohort (OC), and propensity score-matched cohort (PSMC) were analyzed. In the OC, 71 and 24 patients received SA and S-1, respectively. The time to relapse (TTR), DFS, and overall survival were better in the S-1 group, but the difference was not significant. In the PSMC, 20 patients each received SA and S-1. The TTR was significantly lower in the S-1 group than in the SA group, while the DFS was significantly improved in the former. S-1 adjuvant chemotherapy may be more effective than SA in early-stage OSCC.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia/epidemiologia , Ácido Oxônico/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Tegafur/uso terapêutico , Idoso , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fatores de Tempo
19.
Am J Clin Oncol ; 43(6): 435-441, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251119

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/terapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Quimioterapia de Indução , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/uso terapêutico , Neoplasias Pancreáticas/cirurgia
20.
J Ovarian Res ; 13(1): 33, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32199455

RESUMO

BACKGROUND: Primary ovarian signet-ring cell carcinoma is extremely rare, with only five recent case reports. Almost all reported cases of ovarian signet-ring cell carcinoma have been treated with TC therapy and none have reported regarding the use of S-1/CDDP therapy. We report a case of primary ovarian signet-ring cell carcinoma treated postoperatively with S-1/CDDP therapy. CASE PRESENTATION: We describe a 55-year-old woman diagnosed with stage IB primary ovarian signet-ring cell carcinoma that was treated with S-1/CDDP therapy. Preoperative transvaginal ultrasonography and contrast-enhanced computed tomography (CT) revealed a solid tumor measuring 10 cm in diameter in the pelvis. The tumor marker levels were as follows: CA125, 41.6 U/mL; CA19-9, < 2.0 U/mL; and CEA, 2.2 ng/mL. Ovarian cancer was suspected, and total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. The left ovary was enlarged to greater than fist-sized, and there was a small amount of clear yellow ascites. Histological examination of the left ovary led to the diagnosis of signet-ring cell carcinoma. Histological examination of the right ovary also showed the presence of a signet-ring cell carcinoma. After surgery, upper and lower gastrointestinal endoscopy and positron-emission tomography-CT were performed to search for a possible primary lesion, but none was found. The patient was diagnosed with primary ovarian signet-ring cell carcinoma with FIGO Stage IB (PT1b, NX, M0). As postoperative adjuvant chemotherapy, S-1/CDDP therapy (S-1120 mg/day/body × 14 days, CDDP 50 mg/m2 day 8, q 21 days) was administered for six cycles. There was no recurrence 27 months after the initial treatment. CONCLUSIONS: We considered S-1/CDDP therapy was effective for primary ovarian signet-ring cell carcinoma. This is the first case report of primary ovarian signet-ring cell carcinoma treated with S-1/CDDP therapy in the world.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Biomarcadores Tumorais , Biópsia , Carcinoma de Células em Anel de Sinete/etiologia , Combinação de Medicamentos , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/etiologia , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia/métodos
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