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1.
Support Care Cancer ; 31(12): 632, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37843639

RESUMO

PURPOSE: Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan. METHODS: This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site. RESULTS: In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE. CONCLUSION: There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.


Assuntos
Dor do Câncer , Delírio , Tramadol , Humanos , Analgésicos Opioides/efeitos adversos , Oxicodona , Hidromorfona/efeitos adversos , Dor do Câncer/tratamento farmacológico , Dor do Câncer/epidemiologia , Dor do Câncer/induzido quimicamente , Estudos Prospectivos , Japão/epidemiologia , Prevalência , Estudos Longitudinais , Fentanila , Constipação Intestinal/induzido quimicamente , Náusea/induzido quimicamente , Vômito/induzido quimicamente , Delírio/tratamento farmacológico
2.
Gan To Kagaku Ryoho ; 45(1): 45-50, 2018 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-29362306

RESUMO

Chemotherapy-induced nausea and vomiting(CINV)were prospectively evaluated using MASCC Antiemesis Tool(MAT) in patients with hematological malignancies in our institution. A total of 33 patients receiving 46 chemotherapy courses were evaluated. Although vomiting was not observed in the acute phase, nausea was seen in 22.6% and 32.3% of the patients in the acute and delayed phases, respectively. Thirty percent(25 cases)of the patients receiving highly emetogenic chemotherapy presented nausea in both the phases, while 40%(18 cases)of the patients receiving moderately emetogenic chemotherapy presented nausea in the delayed phase. The oral intake was quantitated retrospectively in 31 patients with non- Hodgkin's lymphoma, who were hospitalized and received CHOP±R. Prior to the initiation of the chemotherapy, 13 patients received the first generation 5-HT3 receptor antagonist granisetron, while 18 patients received the second generation palonosetron. Oral intake was greater in the patients who were administered palonosetron. Thus, the present study suggested that antiemetic treatment could be improved at our institution.


Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Náusea/induzido quimicamente , Vômito/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Retrospectivos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
3.
Rinsho Ketsueki ; 58(12): 2406-2410, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29332875

RESUMO

A 68-year-old male patient, who was diagnosed with MGUS (IgG-λ) 11 years ago, was referred to our hospital because of a progressing pancytopenia. He was diagnosed with multiple myeloma (MM) and was hospitalized because of fever and pneumonia. Although empiric antibiotic and antifungal therapies were promptly initiated, his pneumonia worsened. Chest CT images revealed diffuse interstitial pneumonia. Although bortezomib/dexamethasone therapy was initiated as a treatment for MM and pneumonia, he showed little response. His pneumonia worsened and progressed to acute respiratory distress syndrome. Using mPSL (500 mg/day), sivelestat, and MM treatment switching to lenalidomide/dexamethasone (Rd), his respiratory status and CT findings rapidly improved. He received Rd therapy as an outpatient; however, after the completion of six cycles of therapy, his MM progressed, with a recurrence of pneumonia and high fever again. The onset of pneumonia was closely associated with MM progression. His pneumonia improved by treatment with mPSL half-pulse and MM treatment switching to carfilzomib/Rd. In the present study, we report the case of a patient with myeloma, who presented with multiple interstitial pneumonia, resulting in respiratory failure twice in concordance with myeloma progression.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Mieloma Múltiplo , Idoso , Humanos , Lenalidomida , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/tratamento farmacológico , Recidiva , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Resultado do Tratamento
4.
Rinsho Ketsueki ; 58(5): 433-437, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28592755

RESUMO

A 64-year-old man was diagnosed with acute myeloid leukemia M2 (FLT3-ITD-positive). After induction chemotherapy and four courses of consolidation therapy, he underwent umbilical cord blood transplantation (CBT) in his first remission. He developed acute graft-versus-host disease (skin stage 2) after successful engraftment. On post-transplantation day 147, he was admitted to the hospital suffering from pneumonia. During the treatment, drastic thrombocytopenia was observed on day 251. Both platelet-associated immunoglobulin G and platelet antibody producing B cells were detected, and he was diagnosed with immune thrombocytopenia (ITP). Treatment with prednisolone (1 mg/kg/day), eltrombopag (25 mg/day), and intravenous immunoglobulin (400 mg/kg) was commenced, but there was no improvement in his platelet count. After switching from eltrombopag to romiplostim (350 µg/week), and addition of cyclosporine, the platelet count rapidly elevated to 150,000/µl. ITP after allogenic stem cell transplantation is a rare complication, and it is often refractory to the 1st-line treatment such as steroids. Herein, we report successful treatment using a combination of romiplostim and an immunosuppressive agent in the case of treatment failure in ITP that developed after CBT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Púrpura Trombocitopênica Idiopática/etiologia , Sangue Fetal , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/terapia
5.
Cancer Sci ; 107(7): 1029-38, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27166836

RESUMO

The major mechanism of imatinib (IM) resistance of CML is the reactivation of ABL kinase either through BCR-ABL gene amplification or mutation. We investigated the cytotoxicity of a pan-ABL tyrosine kinase inhibitor, ponatinib, and a pan-histone deacetylase inhibitor, panobinostat, against IM-resistant CML cells in vitro. Two different IM-resistant cell lines, K562/IM-R1 and Ba/F3/T315I were evaluated in comparison with their respective, parental cell lines, K562 and Ba/F3. K562/IM-R1 overexpressed BCR-ABL due to gene amplification. Ba/F3/T315I was transfected with a BCR-ABL gene encoding T315I-mutated BCR-ABL. Ponatinib inhibited the growth of both K562/IM-R1 and Ba/F3/T315I as potently as it inhibited their parental cells with an IC50 of 2-30 nM. Panobinostat also similarly inhibited the growth of all of the cell lines with an IC50 of 40-51 nM. This was accompanied by reduced histone deacetylase activity, induced histone H3 acetylation, and an increased protein level of heat shock protein 70, which suggested disruption of heat shock protein 90 chaperone function for BCR-ABL and its degradation. Importantly, the combination of ponatinib with panobinostat showed synergistic growth inhibition and induced a higher level of apoptosis than the sum of the apoptosis induced by each agent alone in all of the cell lines. Ponatinib inhibited phosphorylation not only of BCR-ABL but also of downstream signal transducer and activator of transcription 5, protein kinase B, and ERK1/2 in both K562/IM-R1 and Ba/F3/T315I, and the addition of panobinostat to ponatinib further inhibited these phosphorylations. In conclusion, panobinostat enhanced the cytotoxicity of ponatinib towards IM-resistant CML cells including those with T315I-mutated BCR-ABL.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Ácidos Hidroxâmicos/farmacologia , Mesilato de Imatinib/farmacologia , Imidazóis/farmacologia , Indóis/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Piridazinas/farmacologia , Acetilação/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Histona Desacetilases/metabolismo , Histonas/metabolismo , Humanos , Panobinostat , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
Cancer Sci ; 107(5): 619-28, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26892864

RESUMO

An increasingly accepted concept is that the progression of colorectal cancer is accompanied by epithelial-mesenchymal transition (EMT). In our study, in order to characterize the properties of EMT in 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumors in vivo, as well as cells cultured in vitro, were immunostained for EMT markers. The immunostaining revealed that seven of the cells had an epithelial phenotype with a high expression of E-cadherin, whereas other cells showed opposite patterns, such as a high expression of vimentin (CX-1, COLO205, CloneA, HCT116, and SW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480, SW620, and COLO320). We evaluated these findings in combination with microarray analyses, and selected five genes: CHST11, SERPINI1, AGR2, FBP1, and FOXA1. Next, we downregulated the expression of SERPINI1 with siRNA in the cells, the results of which showed reverse-EMT changes at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secreted SERPINI1 protein of SW620 cells, which supported the importance of SERPINI1 in EMT. The development of therapeutic strategies targeting EMT is ongoing, including methods targeting the transforming growth factor-ß signaling pathway as well as the Wnt pathway. SERPINI1 is an important regulator of EMT. Our findings help to elucidate the signaling pathways of EMT, hopefully clarifying therapeutic pathways as well.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Modelos Biológicos , Transplante de Neoplasias , Neuropeptídeos/metabolismo , Serpinas/metabolismo , Animais , Caderinas/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Neuropeptídeos/deficiência , Neuropeptídeos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Serpinas/deficiência , Serpinas/genética , Sulfotransferases/deficiência , Sulfotransferases/genética , Sulfotransferases/metabolismo , Vimentina/metabolismo , Via de Sinalização Wnt , Neuroserpina
7.
J Epidemiol ; 26(1): 30-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26567604

RESUMO

BACKGROUND: Few studies have assessed whether treatment of acute cervical spinal cord injury (SCI) patients contributes to depression. METHODS: Using an administrative database, we assessed patients for whom the diagnosis was unspecified injuries of cervical spinal cord (International Classification of Diseases and Injuries-10th (ICD-10) code; S14.1). We categorized patients with codes for depressive episode (ICD-10 code; F32) or recurrent depressive disorder (F33), or those prescribed antidepressants (tricyclic, tetracyclic, Selective Serotonin Reuptake Inhibitors, Serotonin Noradrenaline Reuptake Inhibitors, Trazodone, Sulpiride, or Mirtazapine) as having a depressive state. We compared the rate of each acute treatment between the depressive state group and the non-depressive state group using chi-square tests, and a multiple logistic regression model was used to identify the association between the acute treatment and depressive state. RESULTS: There were 151 patients who were judged to be in a depressive state, and the other 2115 patients were categorized into the non-depressive state group. Intervention of intravenous anesthesia, tracheostomy, artificial respiration, and gastrostomy had a significant positive correlation with depressive state. Multiple logistic regression analysis showed that tracheostomy (odds ratio [OR] 2.18; 95% confidence interval [CI], 1.09-4.38) and artificial respiration (OR 2.28; 95% CI, 1.32-3.93) were significantly associated with depressive state, and men had a 36% reduction in the risk of depressive state compared with women (OR 0.64; 95% CI, 0.44-0.94), whereas age, wound-treatment, all of the orthopedic procedures, intravenous anesthesia, and gastrostomy were not associated with depressive state. CONCLUSIONS: These findings suggest that tracheostomy, artificial respiration and female gender in the acute phase after cervical SCI might be associated with the development of depression.


Assuntos
Depressão/epidemiologia , Traumatismos da Medula Espinal/terapia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Traumatismos da Medula Espinal/psicologia , Adulto Jovem
8.
Gan To Kagaku Ryoho ; 42(12): 1752-4, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805161

RESUMO

A 70-year-old man with a history of myocardial infarction (MI) and taking 2 antiplatelet drugs was diagnosed with anemia his 6-month post-MI checkup. A lower gastrointestinal endoscopy detected ascending colon cancer, and contrast-enhanced a computed tomography scan revealed hilar cholangiocarcinoma as well as lesions suspicious for gastrointestinal stromal tumors of the small intestine. The patient was given a preoperative diagnosis of synchronous triple malignant tumors. The decision to perform a two-stage procedure was made for the following reasons: the impossibility of discontinuing antiplatelet drugs 6 months after drug-eluting stent placement, continuous bleeding due to colon cancer and the possibility of suffering severe stress from surgery while at high risk for diseases such as hepatic failure. In the initial procedure, a right hemicolectomy and surgical resection of the mesenteric tumor (later diagnosed as a liposarcoma) were performed after portal vein embolization. Confirmation of an enlarged residual liver was confirmed 2 months after the initial procedure. The patient underwent right hepatectomy and resection of the extrahepatic bile duct and the biliary tract was surgically reconstructed. Safe resection of tumors was successfully performed by choosing a two-stage procedure for triple malignancy, including hilar cholangiocarcinoma, ascending colon cancer, and liposarcoma, in a single patient.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Colo Ascendente/cirurgia , Neoplasias do Colo/cirurgia , Lipossarcoma/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Extra-Hepáticos/patologia , Colo Ascendente/patologia , Neoplasias do Colo/patologia , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
9.
Gan To Kagaku Ryoho ; 42(12): 2072-4, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805268

RESUMO

A 32-year-old man was admitted to our hospital with the complaint of epigastric pain. Gastrointestinal endoscopy revealed a type 5 advanced gastric cancer at the posterior wall of the antrum. Contrast-enhanced computed tomography (CT) and endoscopic ultrasonography showed a fluid collection, indicating peritoneal metastasis. CEA levels were elevated, at 16.5 ng/mL. A diagnosis was made of cStage Ⅳ (T4aN3H0P1M1), and he underwent first-line chemotherapy using CDDP and S-1. However, this immediately failed with the severe adverse effect of vomiting.Docetaxel and S-1 were adopted as second-line chemotherapy. Since progression of the disease was confirmed after 8 cycles of second-line chemotherapy, nab-paclitaxel was administered as third-line chemotherapy. Despite a trend of increasing CEA after 4 cycles of third-line chemotherapy, CT revealed a tumor volume reduction as well as the disappearance of the fluid collection, after which staging laparoscopy was performed. Based on the finding that non-curative factors such as fluid collection and peritoneal nodules were not observed, distal gastrectomy was performed. Histopathological examination showed a ypStage ⅠA (T1bN0H0P0M0)tumor with a grade 3 therapeutic response to chemotherapy.The patient is currently doing well with no recurrence 11 months after the operation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/sangue , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Terapia Combinada , Gastrectomia , Humanos , Masculino , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
10.
Gan To Kagaku Ryoho ; 42(12): 2169-71, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805300

RESUMO

The case is of a 62-year-old man with no medical history and no family history.A type 2 tumor was found in the entire circumference of the sigmoid colon by colonoscopy after a positive result on a fecal occult blood test, and 5 liver metastases were recognized in both lobes of the liver by using contrast-enhanced CT.He was first treated by primary tumor resection. Subsequently, 5-fluorouracil/l-leucovorin/oxaliplatin (mFOLFOX6) plus bevacizumab (BV) was started 1 month after the surgery and a total of 8 cycles of mFOLFOX6 plus BV were administered without any adverse events.On CT assessment after the chemotherapy, the patient was diagnosed with stable disease according to RECIST guidelines since the size of the tumor only showed a slight reduction.However, it was considered to be an optimal response based on the morphologic criteria. Thereafter, a medial segmentectomy and partial resection of the liver was performed.A mucus reservoir was found in the tumor site, and no viable tumor cells were detected pathologically, which confirmed the pathological complete response with mFOLFOX6 plus BV.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/secundário , Neoplasias do Colo Sigmoide/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Colectomia , Terapia Combinada , Fluoruracila/administração & dosagem , Hepatectomia , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgia
11.
Anticancer Res ; 44(3): 981-991, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423659

RESUMO

BACKGROUND/AIM: Methionine metabolism contributes to supplying sulfur-containing amino acids, controlling the methyl group transfer reaction, and producing polyamines in cancer cells. Polyamines play important roles in various cellular functions. Methylthioadenosine phosphorylase (MTAP), the key enzyme of the methionine salvage pathway, is reported to be deficient in 15-62% of cases of hematological malignancies. MTAP-deficient cancer cells accumulate polyamines, resulting in enhanced cell proliferation. The aim of this study was to investigate the combined effects of the polyamine synthesis inhibitor SAM486A and the anticancer antimetabolite cytarabine in MTAP-deficient leukemic cells in vitro. MATERIALS AND METHODS: The leukemia cell line U937 and the subline, U937/MTAP(-), in which MTAP was knocked down by shRNA, were used. The experiments were performed in media supplemented with 20% methionine (low methionine), which was the minimum concentration for maintaining cellular viability. RESULTS: The knockdown efficiency test confirmed a 70% suppression of the expression of the MTAP gene in U937/MTAP(-) cells. Even in the media with low methionine, the intracellular methionine concentration was not reduced in U937/MTAP(-) cells, suggesting that the minimum supply of methionine was sufficient to maintain intracellular levels of methionine. Both U937/MTAP(+) and U937/MTAP(-) cells were comparably sensitive to anticancer drugs (cytarabine, methotrexate, clofarabine and 6-thioguanine). The combination of SAM486A and cytarabine was demonstrated to have synergistic cytotoxicity in U937/MTAP(-) cells with regard to cell growth inhibition and apoptosis induction, but not in U937/MTAP(+) cells. Mechanistically, SAM486A altered the intracellular polyamine concentrations and reduced the antiapoptotic proteins. CONCLUSION: Methionine metabolism and polyamine synthesis can be attractive therapeutic targets in leukemia.


Assuntos
Amidinas , Antineoplásicos , Indanos , Leucemia , Humanos , Citarabina/farmacologia , Purina-Núcleosídeo Fosforilase/genética , Purina-Núcleosídeo Fosforilase/metabolismo , Poliaminas , Metionina/farmacologia , Metionina/metabolismo , Leucemia/tratamento farmacológico
12.
Int J Hematol ; 119(6): 677-685, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38519820

RESUMO

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Progressão da Doença , Fluordesoxiglucose F18 , Linfoma Folicular , Tomografia por Emissão de Pósitrons , Rituximab , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/mortalidade , Cloridrato de Bendamustina/administração & dosagem , Rituximab/administração & dosagem , Fluordesoxiglucose F18/administração & dosagem , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Japão , Tomografia por Emissão de Pósitrons/métodos , Recidiva , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos/administração & dosagem
13.
Cancer Sci ; 103(9): 1722-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22632031

RESUMO

Gemtuzumab ozogamicin (GO) consists of the CD33 antibody linked to calicheamicin. The binding of GO to the CD33 antigen on leukemic cells results in internalization followed by the release of calicheamicin, thereby inducing DNA strand breaks. We hypothesized that the induction of DNA strand breaks would be a surrogate marker of GO cytotoxcity. Here, two GO-resistant variants (HL/GO-CSA [225-fold], HL/GO [200-fold]) were established by serially incubating human leukemia HL-60 cells with GO with or without a P-glycoprotein (P-gp) inhibitor, cyclosporine A, respectively. The CD33 positivity was reduced in both variants. The HL/GO-CSA cells showed an increased multidrug resistance protein-1 (MRP1) transcript, and an MRP1 inhibitor partially reversed GO resistance. The HL/GO cells had neither P-gp nor MRP1 overexpression. Microarray analysis and Western blotting indicated elevated levels of DNA repair-associated proteins in both variants. Two other leukemic subclones, showing either P-gp or MRP1 overexpression, were also GO-resistant. Using single cell gel electrophoresis analysis, it was determined that GO-induced DNA strand breaks increased dose-dependently in HL-60 cells, whereas the number of breaks was reduced in the GO-resistant cell lines. The induction of DNA strand breaks was correlated with GO sensitivity among these cell lines. The CD33 positivity and the expression levels of transporters were not proportional to drug sensitivity. Using primary leukemic cells, the induction of DNA strand breaks appeared to be associated with GO sensitivity. Thus, GO-induced DNA strand breaks as the final output of the mechanism of action would be critical to predict GO cytotoxicity.


Assuntos
Aminoglicosídeos/toxicidade , Anticorpos Monoclonais Humanizados/toxicidade , Antineoplásicos/toxicidade , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Leucemia/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antineoplásicos/uso terapêutico , Reparo do DNA , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Gemtuzumab , Expressão Gênica , Células HL-60 , Humanos , Células K562 , Leucemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Prognóstico , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico , Adulto Jovem
14.
Tohoku J Exp Med ; 227(4): 237-44, 2012 08.
Artigo em Inglês | MEDLINE | ID: mdl-22820613

RESUMO

Acute cholecystitis is one of the most frequently encountered conditions in daily practice in Japan. However, there is a shortage of detailed data about treatments that have been performed according to the clinical practice guidelines (CPGs) for acute cholecystitis. We therefore examined the management of acute cholecystitis for adherence to the appropriate CPGs using the Japanese administrative database associated with the Diagnosis Procedure Combination (DPC) system. We collected data from 6,070 patients with acute cholecystitis, examining for the application of four recommended treatments (administration of antimicrobial drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) and performance of early and laparoscopic cholecystectomy). The patients were classified according to the procedures documented for each case: no gallbladder drainage (n = 4,333), gallbladder drainage without supportive care (ventilation or hemodiafiltration or the use of vasopressor) (n = 1,591) and gallbladder drainage and supportive care (n = 146). Multiple logistic regression models revealed that patients with gallbladder drainage without supportive care and those with gallbladder drainage and supportive care significantly higher received administration of antimicrobial drugs and NSAIDs, while these patients underwent less early or laparoscopic cholecystectomy than did patients without gallbladder drainage, after adjusting for potential confounding effects of the clinical variables. This study demonstrated that there were various differences with regard to the performance of recommended treatments between the levels of procedures required for acute cholecystitis. In addition, this administrative database was a feasible tool for the evaluation of care processes and will provide useful information contributing to improved quality of medical care.


Assuntos
Colecistite Aguda/terapia , Bases de Dados como Assunto/organização & administração , Guias de Prática Clínica como Assunto , Adulto , Feminino , Diretrizes para o Planejamento em Saúde , Humanos , Japão , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
15.
Int J Hematol ; 113(3): 362-369, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33219461

RESUMO

We retrospectively evaluated the clinical efficacy and toxicity of gemtuzumab ozogamicin (GO) in patients with relapsed acute myeloid leukemia (AML). Nineteen patients (median 70 years) received GO (9 mg/m2, days 1 and 15) as salvage therapy in our institution between 2006 and 2017. The primary endpoint was the response rate. The secondary endpoint was the occurrence of adverse events. Thirteen patients had de novo AML, and 6 patients had secondary AML. Most of the patients had received salvage treatments more than once prior to GO. Six patients responded to the treatment (31.6%) with 3 complete remissions (15.8%). Five patients had stable disease, and 8 patients did not show any response. GO was more efficacious among the patients with fewer numbers of prior salvage treatments. CD33 positivity of leukemic cells was higher in responders than in nonresponders. Peripheral WT1 mRNA levels mostly decreased over time in the responders. The adverse event most commonly seen was febrile neutropenia (84%). No patient presented with veno-occlusive disease. Three patients died by day 30 (mortality rate 15.8%), one due to acute respiratory distress syndrome and the other two due to sepsis. GO remains an effective salvage treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Gemtuzumab/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Avaliação de Medicamentos , Neutropenia Febril/induzido quimicamente , Feminino , Gemtuzumab/efeitos adversos , Genes do Tumor de Wilms , Hematoma Subdural/etiologia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Recidiva , Indução de Remissão , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Proteínas WT1/biossíntese
16.
Lancet Haematol ; 8(12): e902-e911, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34826413

RESUMO

BACKGROUND: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are commonly initiated in older patients with chronic myeloid leukaemia in the chronic phase at standard doses. However, because of their safety profile in this population, appropriate therapy has not been established. We aimed to investigate whether a lower than standard dose of dasatinib was an appropriate therapy for older patients with chronic myeloid leukaemia in the chronic phase. METHODS: DAsatinib, Very Low-dose, for Elderly CML-CP patients (DAVLEC) was a multicentre, single-arm, phase 2 trial done in 25 Japanese hospitals. We enrolled patients older than 70 years with newly diagnosed chronic myeloid leukaemia in the chronic phase, ECOG performance status 0-2, and no previous treatment for CML other than hydroxyurea within 4 weeks. Second-generation TKI dasatinib was given orally at a starting dose of 20% of the standard dose (20 mg/day). If the treatment was assessed as optimal response at 3 months, 6 months, and 9 months and adverse events were grade 2 or better (according to the NCI Common Toxicity Criteria v 4.0), the same dose was continued. If response was suboptimal and adverse events were grade 2 or better, the dose was increased by 20 mg/day. Once a dose reduction had been made because of a grade 3 or worse adverse event, there were no further dose increases. Treatment was discontinued if assessed as failure (disease progression to the accelerated phase or acute phase). The primary endpoint was the achievement of major molecular response at 12 months, assessed using a per-protocol analysis. This trial is registered at with the UMIN clinical trial registry, UMIN000024548, and has completed its planned observation period. FINDINGS: Between Nov 1, 2016, and Oct 30, 2019, 52 patients received first-line dasatinib therapy at 20 mg/day. The median age at diagnosis was 77·5 years (73·5-83·0). 35 (67%) patients were male and 17 (33%) were female. 31 (60%) of 52 patients reached major molecular response at 12 months (one-sided 95% CI 48-71), with a median follow-up of 366 days (IQR 353-372). Grade 3-4 adverse events were reported in 12 (23%) patients. Neutropenia was the most frequent grade 3-4 adverse event, occurring in three (6%) patients. No treatment-related deaths were observed. INTERPRETATION: Low-dose dasatinib at 20mg/day is worthy of consideration as a starting dose for older patients with newly diagnosed chronic myeloid leukaemia in the chronic phase. However, this dose needs to be further studied in a larger cohort and with a more ethnically diverse population. FUNDING: Bristol-Myers Squibb.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Idoso , Dasatinibe/efeitos adversos , Esquema de Medicação , Feminino , Proteínas de Fusão bcr-abl , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Resultado do Tratamento
17.
Medicine (Baltimore) ; 97(44): e12981, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30383650

RESUMO

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.


Assuntos
Coagulação Intravascular Disseminada/tratamento farmacológico , Gabexato/uso terapêutico , Leucemia Mieloide Aguda/complicações , Trombomodulina/uso terapêutico , Adolescente , Idoso , Idoso de 80 Anos ou mais , Coagulação Intravascular Disseminada/etiologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinogênio , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Curr Probl Cancer ; 41(6): 419-425, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29061362

RESUMO

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma/tratamento farmacológico , Morfolinas/uso terapêutico , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Adulto , Idoso , Anorexia/sangue , Anorexia/induzido quimicamente , Anorexia/tratamento farmacológico , Antieméticos/uso terapêutico , Aprepitanto , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Feminino , Granisetron/uso terapêutico , Humanos , Linfoma/sangue , Masculino , Pessoa de Meia-Idade , Náusea/sangue , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Prednisona/efeitos adversos , Receptores da Neurocinina-1/metabolismo , Substância P/sangue , Substância P/metabolismo , Vincristina/efeitos adversos , Vômito/sangue , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
19.
Intern Med ; 56(18): 2407-2413, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28824057

RESUMO

Objective We retrospectively compared the clinical efficacy and toxicity of rituximab (R)-THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone) with that of R-CHOP (rituximab, adriamicin, cyclophosphamide, vincristine, and prednisolone) in previously untreated old patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients admitted to our institution between 2004 and 2013 were examined. The patients received either R (375 mg/m2, day 1)-THP-COP (pirarubicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5) or R-CHOP (adriamicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5). The doses of chemotherapeutic agents were adjusted depending on the patient's age and associated complications. The treatment was performed for 6 to 8 cycles. Results Among 74 patients with DLBCL (median 76, range 65-90 years; male 39, female 35), 29 received R-THP-COP, while 45 received R-CHOP. The overall response rates were 94.6% (complete response 86.4%, partial response 8.1%). The 2-year overall and progression-free survival rates were 77.6% and 68.5% for the R-THP-COP regimen and 79.2% and 78.9% for R-CHOP, respectively. No significant differences were found between these two regimens regarding the clinical efficacies. The most frequent adverse event was neutropenia (72.4% for the R-THP-COP regimen, 88.9% for the R-CHOP regimen). The cardiac function as evaluated by ejection fraction values was not impaired in either regimen. Conclusion R-THP-COP was effective and safe as an alternative to R-CHOP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Neutropenia/induzido quimicamente , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
20.
Anticancer Res ; 36(12): 6655-6662, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27919998

RESUMO

BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy. PATIENTS AND METHODS: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated. RESULTS: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens. TLS occurred in 13 (10.5%) out of 124 chemotherapy courses with five (4.0%) cases of laboratory TLS and eight (6.5%) cases of clinical TLS. The incidences of TLS were 17.5% for bortezomib-containing regimens and 3.2% for non-bortezomib-based regimens. No TLS occurred in the patients treated with IMiD-containing regimens. TLS occurred more frequently in the patients with elevated uric acid, creatinine, or beta-2-microglobulin levels at baseline. The patients with disease classified as advanced International Staging System also developed TLS more frequently. All the patients who developed clinical TLS received bortezomib-containing regimens (8/63, 12.7%). Among them, patients with elevated values of uric acid or creatinine developed clinical TLS more often than those without such elevation. The incidence of clinical TLS was 33.3% if the patients had renal dysfunction at baseline and were subsequently treated with bortezomib-based regimens (8/24 cases). CONCLUSION: Patients with renal dysfunction or a high uric acid level receiving bortezomib-based chemotherapy have a high risk of developing TLS.


Assuntos
Bortezomib/uso terapêutico , Nefropatias/tratamento farmacológico , Mieloma Múltiplo/complicações , Síndrome de Lise Tumoral/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade
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