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1.
Gan To Kagaku Ryoho ; 48(11): 1365-1368, 2021 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-34795128

RESUMO

Docetaxel and cyclophosphamide (TC) and epirubicin and cyclophosphamide (EC) therapies are postoperative chemotherapy regimens for breast cancer. However, a previous study reported on the development of adverse events, such as neutropenia, in Asian patients. In this study, we examined the occurrence of neutropenia during chemotherapy, assessed the symptoms, and investigated the dose-reduction/discontinuation of chemotherapy or admission in patients undergoing postoperative EC or TC therapy following breast cancer surgery at our hospital between April 2018 and March 2020. EC and TC therapies were performed in 29 and 23 patients, respectively. We observed a significant difference in the incidence of neutropenia between the two therapies, although this observation might have been influenced by the frequent use of pegfilgrastim. In the TC therapy group, edema and pain were frequently observed. We observed no significant differences in the dose-reduction/discontinuation of chemotherapy or admission. However, in the TC therapy group, 5 patients required admission.


Assuntos
Neoplasias da Mama , Neutropenia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Epirubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hospitais Urbanos , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/epidemiologia , Resultado do Tratamento
2.
Lancet Haematol ; 8(11): e818-e827, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34634256

RESUMO

BACKGROUND: Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) is a front-line treatment for patients with aggressive B-cell lymphomas. Bcl-2 is associated with chemoresistance due to BCL2 gene rearrangement or protein overexpression and is antagonised by venetoclax. We aimed to assess the safety of venetoclax with dose-adjusted EPOCH-R as initial therapy in aggressive B-cell lymphoma. METHODS: We conducted a single-arm, phase 1 study across seven treatment centres in the USA. Eligible patients were aged 18-80 years with histologically confirmed, previously untreated diffuse large B-cell lymphoma, transformed indolent non-Hodgkin lymphoma, high-grade B-cell lymphoma with double-hit or not otherwise specified, or primary mediastinal B-cell lymphoma, with Ann Arbor stage II-IV and Eastern Cooperative Oncology Group performance status of 0-2. Participants received six cycles of oral venetoclax 400 mg, 600 mg, or 800 mg once daily for 10 days per cycle with dose-adjusted EPOCH-R (one cycle every 3 weeks; baseline doses were intravenous rituximab 375 mg/m2 on day 1, intravenous etoposide 50 mg/m2 on days 1-4, oral prednisone 60 mg/m2 twice daily on days 1-5, intravenous vincristine 0·4 mg/m2 on days 1-4, intravenous cyclophosphamide 750 mg/m2 on day 5, and intravenous doxorubicin 10 mg/m2 on days 1-4). A subsequent cohort received venetoclax 600 mg once daily for 5 days per cycle. The primary endpoints were the maximum tolerated dose, dose-limiting toxicities, and the recommended phase 2 dose of venetoclax. Analyses were done per protocol. This trial is registered with ClinicalTrials.gov, NCT03036904, and enrolment is now closed. FINDINGS: Between Feb 3, 2017, and June 4, 2019, 34 patients were assessed for eligibility, and 30 were enrolled and received venetoclax with dose-adjusted EPOCH-R. The median patient age was 64·0 years (IQR 51·6-69·4). The maximum tolerated dose was 800 mg for 10 days and the established recommended phase 2 dose was 600 mg for 5 days due to tolerability for treatment duration. One (3%) of 30 patients had a dose-limiting toxicity in cycle one (grade 4 thrombocytopenia with 800 mg dose). The most common grade 3-4 adverse events were cytopenias (28 [93%] of 30 patients); febrile neutropenia occurred in 19 (63%) patients. Grade 3-4 non-haematological adverse events included hypophosphataemia (n=10), hypokalaemia (n=7), and hyperglycaemia (n=5). Serious adverse events included infection (n=7) and gastrointestinal toxicities including abdominal pain (n=3), colonic perforation (n=1), and small intestinal obstruction (n=1). There was one treatment-related death (sepsis). Overall response rate was 96·7% (95% CI 82·8-99·9); 28 (93·3% [77·9-99·2]) of 30 patients had complete response and one (3·3% [0·1-17·2]) had a partial response. INTERPRETATION: Venetoclax with dose-adjusted EPOCH-R showed an acceptable safety profile at the recommended phase 2 dose and had encouraging preliminary activity in this population at high risk of adverse outcomes, and is worthy of further study. The combination is being investigated in Alliance 051701 (NCT03984448). FUNDING: Genentech.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Linfoma de Células B/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico
3.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641277

RESUMO

The effects of immunomodulatory activity of two types of carboxymethyl pachymaran (CMP-1 and CMP-2) on cyclophosphamide (CTX)-induced mice were investigated. Both CMP-1 and CMP-2 were found to restore the splenomegaly and alleviate the spleen lesions and the mRNA expressions of TLR4, MyD88, p65 and NF-κB in spleen were also increased. CMP-1 and CMP-2 could enhance the immunity by increasing the levels of TNF-α, IL-2, IL-6, IFN-γ, Ig-A and Ig-G in serum. In addition, CMP-1 could increase the relative abundance of Bacteroidetes and reduce the relative richness of Firmicutes at the phylum level. CMP-1 and CMP-2 could reduce the relative abundance Erysipelatoclostridum at the genus level. CMP-1 and CMP-2 might enhance the immune function of immunosuppression mice by regulating the gene expression in the TLR4/NF-κB signaling pathway and changing the composition and abundance of the intestinal microbiota. The results suggested that CMP-1 and CMP-2 would be as potential immunomodulatory agents in functional foods.


Assuntos
Ciclofosfamida/efeitos adversos , Glucanos/química , Hospedeiro Imunocomprometido/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Polissacarídeos/administração & dosagem , Esplenomegalia/tratamento farmacológico , Animais , Bacteroidetes/classificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Modelos Animais de Doenças , Feminino , Firmicutes/classificação , Firmicutes/genética , Firmicutes/isolamento & purificação , Alimento Funcional , Microbioma Gastrointestinal/efeitos dos fármacos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Filogenia , Polissacarídeos/química , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Esplenomegalia/induzido quimicamente , Esplenomegalia/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética
5.
Nutrients ; 13(9)2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34579145

RESUMO

Short-term calorie reduction (SCR) requires individuals to reduce their calorie intake to less than 50% of normal requirements and has shown good tolerance and potential benefits in prior studies addressing gynecological cancer patients. More studies are needed to further confirm its safety, feasibility, and effects in patients with different cancers, including hematological malignancies. This pilot cohort study with a matched-pair comparison group was registered at ClinicalTrails.gov [201810112RIND]. Adult patients diagnosed with advanced-stage diffuse large-B cell lymphoma were recruited (SCR group) and matched with one comparison patient (comparison group), each in a manner blinded to their outcomes. The SCR group undertook at least two cycles of 48 h water fast along with their chemotherapy R-CHOP. Descriptive analysis and generalized estimating equations were used to analyze the data. Six participants completed multiple cycles of SCR and were compared to their six counterparts in the comparison group. The results showed that SCR is safe and feasible in terms of a high compliance rate and stable nutritional status. The SCR was associated with benefits in post-chemotherapy hematological parameters (i.e., erythrocyte [p < 0.001] and lymphocyte counts [p < 0.001]). More randomized controlled trials are needed to validate the effects of SCR on different types of cancer populations.


Assuntos
Restrição Calórica/métodos , Quimioterapia de Indução/métodos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Restrição Calórica/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Estudos de Viabilidade , Feminino , Humanos , Linfoma Difuso de Grandes Células B/dietoterapia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Projetos Piloto , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico
6.
FASEB J ; 35(10): e21952, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34555210

RESUMO

Cyclophosphamide (CP) has been widely used in the treatment of various malignancies and autoimmune diseases, but acrolein, a byproduct of CP, causes severe hemorrhagic cystitis as the major side effect of CP. On the other hand, a large amount of prostacyclin (PGI2 ) is produced in bladder tissues, and PGI2 has been shown to play a critical role in bladder homeostasis. PGI2 is biosynthesized from prostaglandin (PG) H2 , the common precursor of PGs, by PGI2 synthase (PTGIS) and is known to also be involved in inflammatory responses. However, little is known about the roles of PTGIS-derived PGI2 in bladder inflammation including CP-induced hemorrhagic cystitis. Using both genetic and pharmacological approaches, we here revealed that PTGIS-derived PGI2 -IP (PGI2 receptor) signaling exacerbated CP-induced bladder inflammatory reactions. Ptgis deficiency attenuated CP-induced vascular permeability and chemokine-mediated neutrophil migration into bladder tissues and then suppressed hemorrhagic cystitis. Treatment with RO1138452, an IP selective antagonist, also suppressed CP-induced cystitis. We further found that cystitis-related nociceptive behavior was also relieved in both Ptgis-/- mice and RO1138452-treated mice. Our findings may provide new drug targets for bladder inflammation and inflammatory pain in CP-induced hemorrhagic cystitis.


Assuntos
Ciclofosfamida/efeitos adversos , Cistite/induzido quimicamente , Cistite/prevenção & controle , Epoprostenol/deficiência , Dor/prevenção & controle , Bexiga Urinária , Animais , Permeabilidade Capilar/efeitos dos fármacos , Células Cultivadas , Quimiotaxia de Leucócito , Cistite/complicações , Sistema Enzimático do Citocromo P-450/deficiência , Progressão da Doença , Epoprostenol/metabolismo , Feminino , Hemorragia/complicações , Hemorragia/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/citologia , Tamanho do Órgão/efeitos dos fármacos , Dor/induzido quimicamente , Dor/complicações , Prostaglandina-E Sintases , Bexiga Urinária/efeitos dos fármacos
7.
Trials ; 22(1): 530, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380536

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up. METHODS/DESIGN: This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test. DISCUSSION: Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20-35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02936375 . Registered on October 18, 2016.


Assuntos
Azatioprina , Nefrite Lúpica , Azatioprina/efeitos adversos , Cromonas , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Sulfonamidas , Resultado do Tratamento
8.
Int J Clin Pharmacol Ther ; 59(10): 645-653, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34338191

RESUMO

OBJECTIVE: The aim of the present study was to compare the effectiveness and safety of rituximab, mycophenolate mofetil (MMF), and cyclophosphamide (CYC) for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS AND METHODS: We conducted a Bayesian network meta-analysis to incorporate direct and indirect data from six randomized controlled trials (comprising 541 patients) that investigated the effectiveness and safety of rituximab, MMF, and CYC for the treatment of patients with AAV and met the inclusion criteria. RESULTS: Rituximab and MMF demonstrated a trend toward a higher response rate than CYC, (OR 1.41, 95% credible interval (CrI) 0.84 - 2.40) and (OR 1.20, % CrI 0.73 - 1.93), respectively. The surface under the cumulative ranking curve (SUCRA) revealed that rituximab has the highest probability of being a better remission-induction therapy (SUCRA = 0.797), followed by MMF and CYC (-SUCRA = 0.537 and 0.166, respectively). However, CYC displayed a propensity for a lower relapse than rituximab and MMF (OR 0.81, 95% CrI 0.42 - 1.50; OR 0.72, % CrI 0.39 - 1.27), further confirmed by -SUCRA rankings. Rating likelihood based on -SUCRA revealed that rituximab was more likely to be the safest medication since it displayed a lower incidence of serious adverse effects (SAEs), followed by CYC and MMF. CONCLUSION: Rituximab may serve as an effective remission-induction therapy for patients with AAV and decrease the incidence of SAEs. Although rituximab showed a high relapse rate, the accompanying desirable safety profile indicates that it is the first therapeutic choice for patients with AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Teorema de Bayes , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Funções Verossimilhança , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Rituximab/efeitos adversos , Resultado do Tratamento
9.
Ann Hematol ; 100(11): 2745-2754, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34333665

RESUMO

The Vulnerable Elders Survey-13 (VES-13) is a well-studied simplified frailty screening tool for elderly patients in the oncology setting. We conducted a prospective clinical trial to evaluate the efficacy and safety of dose-adjusted treatment based on the VES-13 in transplant-ineligible patients with newly diagnosed multiple myeloma (MM). In the Fit group (VES-13 <3), patients were treated with 4 cycles of standard-dose VCD (bortezomib, cyclophosphamide, and dexamethasone) followed by 4 cycles of standard-dose VTD (bortezomib, thalidomide, and dexamethasone). In the Frail group (VES-13 ≥3), patients were treated with 4 cycles of reduced-dose VCD followed by 4 cycles of reduced-dose VTD. The median age was 75 years (66-86 years), and 34% of the cases were classified as PS 3. Among the Fit group (n=16), the overall response rate (ORR) was 87.5%. Among the Frail group (n=31), the ORR was 87.1%. There were no significant differences in progression-free survival (PFS) and overall survival (OS) between the Fit and Frail groups (3-year PFS: 68.8% vs 53.3%, P = 0.658; 3-year OS: 70.0% vs 77.6%, P = 0.919). Personalized VCD-VTD sequential therapy based on the VES-13 was associated with high response rates and showed acceptable safety in elderly frail patients with MM. The study is registered as UMIN000011235.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso Fragilizado , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Hiponatremia/induzido quimicamente , Japão , Estimativa de Kaplan-Meier , Masculino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Medicina de Precisão , Intervalo Livre de Progressão , Estudos Prospectivos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
10.
Thromb Res ; 206: 111-119, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34455128

RESUMO

INTRODUCTION: Leukocytes are found in organizing thrombi and are associated with thrombus growth. However, their role in the initial stage of thrombus formation is not well known. We investigated the role of leukocytes in the early stage of arterial thrombosis by inducing leukopenia. METHODS: In this double-blind, randomized, placebo-controlled study, 72 Institute of Cancer Research mice were randomly treated with intraperitoneal 100 mg/kg cyclophosphamide or normal saline. The primary outcome was time to occlusion after FeCl3 treatment. We also compared thrombus size, histological composition, and association with peripheral blood cell counts between cyclophosphamide and control groups. RESULTS: Cyclophosphamide treatment significantly decreased leukocyte counts by 82.8% compared to placebo (P < 0.001). The time to occlusion was significantly longer in the cyclophosphamide group (3.31 ± 1.59 min) than in the control group (2.30 ± 1.14 min; P = 0.003). The immunoreactivity for Ly6G-positive cells, intracellular histone H3, and released histone H3 in thrombi was significantly reduced in the cyclophosphamide group by 92.8%, 50.2%, and 34.3%, respectively. Time to occlusion had a moderate negative correlation with leukocyte count in peripheral blood (r = -0.326, P = 0.022) in the entire group. CONCLUSIONS: Cyclophosphamide-induced leukopenia attenuated thrombus formation during the early stage of arterial thrombosis. Our findings suggest the potential role of leukocytes in the initial stage of arterial thrombosis.


Assuntos
Leucopenia , Trombose , Animais , Ciclofosfamida/efeitos adversos , Contagem de Leucócitos , Leucócitos , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico , Camundongos , Trombose/induzido quimicamente , Trombose/tratamento farmacológico
11.
Medicine (Baltimore) ; 100(28): e26628, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260552

RESUMO

OBJECTIVE: The objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus cyclophosphamide (CTX)-corticosteroid combination therapy in idiopathic membranous nephropathy (IMN) patients. METHODS: Databases including the PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from inception to October 20, 2020. Eligible studies comparing TAC monotherapy and CTX-corticosteroid combination therapy in IMN patients were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Nine studies were included in the meta-analysis. One randomized controlled trial and eight cohort studies involving 442 patients were identified. Compared with CTX-corticosteroid combination therapy for IMN, TAC monotherapy had higher complete remission (CR) at month 6 (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.35-3.50, P < .01). The 2 therapeutic regimens had similar partial remission (OR 0.69, 95% CI 0.45-1.04, P = .08), total remission (OR 1.38, 95% CI 0.85-2.23, P = 0.19) at month 6, and similar CR (OR 1.64, 95% CI 0.84-3.19, P = .15), partial remission (OR 0.71, 95% CI 0.37-1.38, P = 0.31), and total remission (OR 1.29, 95% CI 0.55-3.01, P = .56) after 1 year. The relapse rate of the TAC group was higher than that of the CTX group, but the difference was not statistically significant (OR 1.85, 95% CI 0.75-4.53, P = .18). There was no difference between the 2 therapeutic regimens concerning glucose intolerance (OR 1.15, 95% CI 0.61-2.14, P = .67), acute renal failure (OR 1.14, 95% CI 0.39-3.33, P = .81), or tremors (OR 4.39, 95% CI 0.75-25.67, P = .10). Incidences of gastrointestinal symptoms (OR 0.29, 95% CI 0.10-0.79, P = .02), infection (OR 0.18, 95% CI 0.08-0.39, P < 0.01), leukopenia (OR 0.14, 95% CI 0.04-0.51, P < .01), and abnormal aminotransferase (OR 0.31, 95% CI 0.13-0.77, P = .01) in the TAC group were all lower than those in the CTX group. Subgroup analysis showed that there was no significant difference between the TAC group and the CTX combined with corticosteroid 0.8 to 1 mg/kg/day group concerning CR at month 6 (P > .05). There was no significant difference between the TAC group and the CTX combined with corticosteroid 0.5 mg/kg/day group concerning abnormal aminotransferase (P > .05). CONCLUSION: TAC monotherapy is comparable to CTX-corticosteroid combination therapy for renal remission in IMN patients. TAC monotherapy had a higher CR in the early stage and had fewer drug-related adverse effects. The relapse rate of TAC monotherapy was higher than that of CTX-corticosteroid combination therapy, but the difference was not significant.


Assuntos
Corticosteroides/uso terapêutico , Ciclofosfamida/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Quimioterapia Combinada , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Indução de Remissão , Tacrolimo/efeitos adversos
12.
Anticancer Res ; 41(8): 3899-3904, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281852

RESUMO

BACKGROUND/AIM: This phase II trial evaluated the efficacy and safety of neoadjuvant nab-paclitaxel plus cyclophosphamide (CPA) plus trastuzumab (AbraC-HER) in patients with early HER2-positive breast cancer. PATIENTS AND METHODS: This was a single-arm, open-label, single-center prospective phase II study. The primary endpoint was pathological complete response rate (pCR rate). The secondary endpoints were clinical antitumor efficacy and the frequency and severity of adverse events. RESULTS: Fifty-nine patients were enrolled in this study. pCR (ypT0/is ypN0) was achieved in 29 patients (49%). The overall response rate was 88.1% (52/59) in all patients. Dose reductions because of adverse events occurred in 3 patients (5.1%) and relative dose intensity was 98%. Compared to Abra-HER, AbraC-HER induced fewer adverse effects. CONCLUSION: Treatment with nab-paclitaxel plus CPA plus trastuzumab was tolerable and effective with a high pCR rate. This AbraC-HER neoadjuvant therapy may be a feasible new treatment option for patients with early HER2-positive breast cancer.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Paclitaxel/uso terapêutico , Trastuzumab/uso terapêutico , Adulto , Idoso , Albuminas/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/efeitos adversos , Receptor ErbB-2 , Trastuzumab/efeitos adversos
13.
Korean J Intern Med ; 36(5): 1181-1189, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34265889

RESUMO

BACKGROUND/AIMS: Febrile neutropenia (FN) interferes with the proper chemotherapy dose density or intensity in non-Hodgkin's lymphoma (NHL) patients. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab has an intermediate FN risk. Prophylactic granulocyte colony-stimulating factor (G-CSF) support is recommended for patients with other host-related risk factors. METHODS: We evaluated the risk factors for FN-related admission in NHL patients who have received primary G-CSF (lenograstim) prophylaxis. RESULTS: Data from 148 patients were analyzed. The incidence of neutropenic fever was 96 events (12.2%), and the median period was 3.85 days (range, 0 to 5.9); the median duration of neutropenia was 4.21 days (range, 3.3 to 5.07). Eighty-three FN-related admissions were reported. Advanced age (> 60 years), female sex, a low albumin level, and prednisone use were associated with FN-related admission in multivariable analysis (p = 0.010, p < 0.001, and p = 0.010, respectively). A comparison between diffuse large B-cell lymphoma patients treated with R-CHOP and pegylated G-CSF and those treated with R-CHOP and lenograstim did not reveal significant differences in the FN-related admission rate between the two groups, although the lenograstim-treated group had a higher incidence of severe neutropenia. CONCLUSION: Elderly patients, female patients, and patients with low albumin levels need to be actively followed-up for FN even when primary prophylaxis with G-CSF has been used.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma não Hodgkin , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Vincristina/efeitos adversos
14.
JCO Glob Oncol ; 7: 1199-1205, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34297605

RESUMO

PURPOSE: Major progress has occurred in multiple myeloma (MM) treatment in recent years, but this is not seen in low- and middle-income countries. MATERIALS AND METHODS: We retrospectively assessed the efficacy and safety of cyclophosphamide, thalidomide, and dexamethasone (cyclophosphamide 400 mg/m2 for 5 days, thalidomide 100 mg once daily, if tolerated, and dexamethasone 40 mg once weekly; in 28-day cycles) in patients with newly diagnosed MM treated at our institution between April 2008 and December 2012. Survival outcomes were estimated by the Kaplan-Meier method. RESULTS: Fifty-nine patients were found to meet the selection criteria. Median age was 56 years (27-78). Fifty-nine percent (n = 35) were male. International Staging System three was found in 24%. The median number of treatment cycles was 11 (range 4-12). After a median of 81-month follow-up (range 5-138 months), the overall response rate was 69.5%. The complete response and very good partial response were 5% and 32%, respectively. Median progression-free survival (PFS) was 35 months (95% CI, 18 to 41). The 3-year PFS was 47.4% (95% CI, 34.5 to 59.6) and 5-year PFS was 24.9% (95% CI, 14.4 to 36.9). The median of overall survival (OS) was 81 months (95% CI, 33 to not reached). The 3-year OS was 63.4% (95% CI, 49.2 to 74.6), and 5-year OS was 57.5% (95% CI, 43.2 to 69.4). The most common adverse event was neutropenia (grade 3 and 4, 30.5%). Out of 23 patients eligible for stem-cell transplantation, 10 (43.5%) proceeded with autologous transplantation. Treatment-related deaths occurred in four patients (6.7%). CONCLUSION: Cyclophosphamide, thalidomide, and dexamethasone achieves good response rates with tolerable toxicity, especially in patients age 65 years or younger representing a feasible approach for patients with MM in low-income health care settings.


Assuntos
Mieloma Múltiplo , Talidomida , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/uso terapêutico , Ciclofosfamida/efeitos adversos , Dexametasona/efeitos adversos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Talidomida/efeitos adversos
15.
Arthritis Care Res (Hoboken) ; 73(8): 1061-1070, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34235889

RESUMO

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). METHODS: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.


Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Poliarterite Nodosa/tratamento farmacológico , Reumatologia/normas , Tomada de Decisão Clínica , Consenso , Ciclofosfamida/efeitos adversos , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Medicina Baseada em Evidências/normas , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Autoimmun Rev ; 20(10): 102898, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34274543

RESUMO

OBJECTIVE: To study whether adding repeated 125 mg methyl-prednisolone pulses (MP) to Eurolupus fortnightly intravenous cyclophosphamide (CYC) improves remission of lupus nephritis (LN) compared with recommended schedules. METHODS: Observational comparative study of patients with biopsy-confirmed class III, IV or V LN: 30 in the mycophenolate (MMF) group, 25 in the CYC group and 38 in the CYC-MP group. The main efficacy outcome was complete response at 12 months. RESULTS: Patients in the CYC-MP group received lower doses of prednisone within 6 months (mean 8.5 mg/d, vs. 15 mg/d in the MMF group vs. 24 mg/d in the CYC group, respectively). The complete response rates at 12 months were: CYC-MP 86%; CYC 56%; MMF 47% (p = 0.002) at Pr/Cr <0.5; CYC-MP 86%; CYC 65%; MMF 63% (p = 0.07) at Pr/Cr ≤0.7. The cumulative 12-month response rates for the CYC-MP, CYC and MMF groups were, respectively, 0.90, 0.58 and 0.63 (p = 0.004). In the adjusted Cox model, patients receiving CYC-MP were more likely to achieve complete response at Pr/Cr <0.5 than those in the MMF (HR vs. CYC-MP 0.33, 95%CI 0.16-0.65) and the CYC groups (HR vs. CYC-MP 0.47, 95%CI 0.21-1.04). Glucocorticoid-related toxicity was seen in 2.6% of the CYC-MP group, 24% of the CYC group and 20% of the MMF group (p = 0.029). CONCLUSION: The addition MP of 125 mg to each fortnightly dose of 500 mg of CYC improves response rates and reduces the need for oral glucocorticoids in patients with class III, IV and V LN.


Assuntos
Nefrite Lúpica , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Quimioterapia de Indução , Nefrite Lúpica/tratamento farmacológico , Metilprednisolona/efeitos adversos , Ácido Micofenólico/uso terapêutico , Estudos Observacionais como Assunto , Indução de Remissão , Resultado do Tratamento
17.
World J Gastroenterol ; 27(20): 2657-2663, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34092982

RESUMO

BACKGROUND: Although cyclophosphamide (CPA) is the key drug for the treatment of autoimmune diseases including vasculitides, it has some well-known adverse effects, such as myelosuppression, hemorrhagic cystitis, infertility, and infection. However, CPA-associated severe enteritis is a rare adverse effect, and only one case with a lethal clinical course has been reported. Therefore, the appropriate management of patients with CPA-associated severe enteritis is unclear. CASE SUMMARY: We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear, lung, and, kidney with positive myeloperoxidase-antineutrophil cytoplasmic antibody. She received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/mo. Ten days after the second course of intravenous CPA, she developed nausea, vomiting, and diarrhea, and was admitted to the hospital. Laboratory testing revealed hypoalbuminemia, suggesting protein-losing enteropathy. Computed tomography revealed wall thickening of the stomach, small intestine, and colon with contrast enhancement on the lumen side. Antibiotics and immunosuppressive therapy were not effective, and the patient's enteritis did not improve for > 4 mo. Because her condition became seriously exhausted, corticosteroids were tapered and supportive therapies including intravenous hyperalimentation, replenishment of albumin and gamma globulin, plasma exchange, and infection control were continued. These supportive therapies improved her condition, and her enteritis gradually regressed. She was finally discharged 7 mo later. CONCLUSION: Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.


Assuntos
Enterite , Granulomatose com Poliangiite , Enteropatias Perdedoras de Proteínas , Ciclofosfamida/efeitos adversos , Enterite/induzido quimicamente , Enterite/diagnóstico , Enterite/tratamento farmacológico , Feminino , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Peroxidase , Enteropatias Perdedoras de Proteínas/induzido quimicamente , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/tratamento farmacológico
18.
Medicine (Baltimore) ; 100(25): e26440, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160436

RESUMO

RATIONALE: Relapsed or refractory acute lymphoblastic leukemia poses a significant clinical challenge due to its poor prognosis, showing survival rates of less than a year even with the use of novel therapies. In this report, we describe the safe and effective use of trametinib combined with dasatinib in a patient with acute lymphoblastic leukemia (ALL). To the best of our knowledge, this is the first report on the successful use of 2 targeted drugs such as trametinib and dasatinib in a pediatric patient with Ph+ ALL and recurrent pancreatitis. PATIENT CONCERNS: A 6-year-old boy with ALL and Philadelphia chromosome (Ph+) who had recurrent asparaginase-associated pancreatitis. DIAGNOSIS: The patient was diagnosed with ALL, based on clinical features, laboratory analyses, bone marrow aspiration evaluation in morphology, immunology, cytogenetics, and molecular. INTERVENTIONS: The patient was treated with dasatinib combined with an intermediate risk-oriented chemotherapy. However, owing to recurrent asparaginase-associated pancreatitis, the patient has to abandon asparaginase in consolidation. Considering the high risk of relapse, we used trametinib and dasatinib combined with chemotherapy as maintenance chemotherapy. OUTCOMES: After 6 months, there were no obvious side effects or residual disease. LESSONS: We suggest that the combination of trametinib and dasatinib may represent a viable option to treat patients with potential relapsed/refractory Ph+ ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dasatinibe/administração & dosagem , Pancreatite/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Criança , Quimioterapia de Consolidação/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Dasatinibe/efeitos adversos , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Resultado do Tratamento
19.
Crit Rev Oncol Hematol ; 163: 103377, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34087342

RESUMO

Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the coexistence of former comorbidities/cardiac issues, especially in the elderly population. Liposome encapsulated drug delivery systems have been adopted to reduce the exposure of normal tissues to the drug, both in solid cancers and lymphomas. Despite claims for lower toxicity, the efficacy of non-pegylated liposome doxorubicin (NPLD) in DLBCL, as compared to standard doxorubicin, has never been established. We systematically reviewed relevant literature of NPLD in lymphoma treatment. Adjusting for age/comorbidities, our metanalysis revealed that the use of combinations including NPLD (R-COMP) were non-inferior in terms of response, overall and progression-free survival to the standard of care (R-CHOP) in overlapping series of DLBCL patients. R-COMP may represent a safe and active option for elderly patients with DLBCL, or for those with some extent of cardiac impairment at baseline.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos
20.
Int J Biol Macromol ; 185: 306-316, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34166692

RESUMO

The study was aimed to investigate the simulated digestion behavior of the bioactive polysaccharides from Chimonanthus nitens Oliv (COP1), antioxidant activity in vitro, and prevention against cyclophosphamide (CP) induced oxidative damage in mice. The results showed that COP1 were 18.843 kDa, and consisted of arabinose (56.6 mol%), galactose (24.9 mol%), xylose (11.1 mol%), and glucose (7.4 mol%). Gastrointestinal digestion significantly improved the radical (DPPH, OH, and ABTS+) scavenging activities of COP1. Meanwhile, administration of COP1 (150, 300, and 600 mg/kg, continuous 16 days) prevented hepatotoxicity in CP-induced mice (reducing liver index and transaminase levels, alleviating liver damage). COP1 also attenuated oxidative stress as evident from as shown by reduced levels of MDA and enhanced activity of antioxidant enzymes (CAT, SOD, and GSH-Px). In addition, COP1 regulated the Nrf2/Keap1 signaling pathway in CP-treated mice, decreasing the upstream factor Keap1 and increasing the upstream factor Nrf2, which in turn enhanced the expression of downstream factors (NQO1, HO-1, GSH-Px, SOD1, and CAT). COP1 also protected the body from CP-induced oxidative damage by down-regulating Bax and caspase3 in the apoptosis pathway and up-regulating Bcl-2 mRNA levels. Overall, COP1 might be harnessed as an effective natural antioxidant for medical and food industries.


Assuntos
Antioxidantes/administração & dosagem , Calycanthaceae/química , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Polissacarídeos/administração & dosagem , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hospedeiro Imunocomprometido , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos
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