Assuntos
Calreticulina/genética , Janus Quinase 2/genética , Trombocitemia Essencial/genética , Adulto , Idoso , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Desnaturação de Ácido Nucleico/genética , Trombocitemia Essencial/patologiaRESUMO
BACKGROUND: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. PATIENTS AND METHODS: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). RESULTS: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. CONCLUSIONS: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status. CLINICAL TRIALS NUMBER: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Cetuximab/administração & dosagem , Desoxicitidina/análogos & derivados , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Cetuximab/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Fenótipo , Modelos de Riscos Proporcionais , Taiwan , Fatores de Tempo , Resultado do TratamentoRESUMO
We investigated the role of activated B cells in thrombopoiesis through the production of interleukin (IL)-1beta and IL-6 in patients with essential thrombocythaemia. The number of B cells did not differ between essential thrombocythaemia patients, irrespective of the presence of Janus activated kinase-2 V617F mutation or wild type, and age-matched healthy adults. However, the number of IL-1beta/IL-6-producing B cells was significantly higher in essential thrombocythaemia patients than that in healthy controls. The relatively high level of IL-1beta/IL-6 production by B cells was associated with serum B cell-activating factor and expression of Toll-like receptor 4 on B cells. A high level of B cell-activating factor was present in essential thrombocythaemia patients with both Janus activated kinase-2 genotypes. Incubation with B cell-activating factor enhanced the expression of Toll-like receptor 4 on B cells. IL-1beta and IL-6 production was not stimulated by B cell-activating factor alone; Toll-like receptor 4 was activated by lipopolysaccharide or patients' sera to produce IL-1beta and IL-6 in B cells. Moreover, essential thrombocythaemia patient B cells facilitated megakaryocyte differentiation when co-cultured with CD34+ haematopoietic stem cells. Antibody neutralisation of IL-1beta and IL-6 attenuated megakaryocyte differentiation. These data suggest that B cells play a crucial role in thrombopoiesis in essential thrombocythaemia patients.
Assuntos
Linfócitos B/imunologia , Plaquetas/fisiologia , Megacariócitos/fisiologia , Trombocitemia Essencial/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Bloqueadores/farmacologia , Fator Ativador de Células B/genética , Fator Ativador de Células B/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/genética , Masculino , Megacariócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Trombocitemia Essencial/genética , Trombopoese/efeitos dos fármacos , Trombopoese/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Regulação para Cima , Adulto JovemRESUMO
The aim of the study was to evaluate the response rate and safety of weekly paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5-fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel 1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2) day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days, followed by a 7-day period without treatment. Treatment was repeated every 21 days. From February 2003 to October 2004, 55 patients were enrolled. The median age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour response, two achieved a complete response and 22 a partial response, with an overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4 toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients (15%). Although treatment was discontinued owing to treatment-related toxicities in nine patients (16%), there was no treatment-related mortality. Weekly paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in treating patients with advanced gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucovorina/efeitos adversos , Paclitaxel/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Estudos Prospectivos , Segurança , Taxa de Sobrevida , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Resultado do Tratamento , Uracila/efeitos adversos , Uracila/uso terapêuticoRESUMO
Expression of CD44s (standard form) in malignant lymphoma is a poor indicator of survival. To investigate whether activation of CD44s can protect from cell death, this study compared the extent of apoptosis induced by chemotherapeutic agents and ionizing radiation (IR) on T-lymphoma cell lines in the presence or absence of adherent hyaluronan and monoclonal antibodies (MoAbs). Growth in the presence of adherent ligands enhanced apoptosis induced by dexamethasone (Dex), but protected cells from epirubicin-induced apoptosis. In IR-induced apoptosis, mouse lymphoma cells had resistance against apoptosis when treated with hyaluronan (HA), although acute cell death reached the same plateau regardless of treatment with adherent MoAbs in human lymphoma cell line. However, the post-irradiated repopulation of lymphoma cells was strikingly accelerated in those treated with CD44 adherent ligands. This repopulation process correlated with the remarkable upregulation of proliferating cell nuclear antigen (PCNA), which is a protein involved in DNA repair. Unscheduled DNA synthesis (UDS), a measure of DNA repair, was consistently enhanced in CD44s-stimulated cells after exposure to radiation. The results suggest that the poor prognostic indication of CD44 expression is more a consequence of enhanced DNA repair following genotoxic damage than of direct resistance to apoptosis.
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Antígenos CD/imunologia , Reparo do DNA/imunologia , Receptores de Hialuronatos/imunologia , Linfoma de Células T/imunologia , Animais , Apoptose , Ciclo Celular , Divisão Celular/efeitos da radiação , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Ligantes , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Camundongos , Análise de SobrevidaRESUMO
To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Sistema Nervoso/efeitos dos fármacos , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Gástricas/patologia , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: We determined the maximum tolerated dose (MTD) and then further evaluated the response rate and safety profile of gemcitabine (Gem) plus doxorubicin (Dox) in chemonaïve patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Dose escalation was tested over four dose levels in each 21-day cycle: level 1 (Gem 1000 mg/m(2) on days 1 and 8, Dox 30 mg/m(2) on day 1), level 2 (Gem/Dox 1250/30), level 3 (Gem/Dox 1250/45) and level 4 (Gem/Dox 1250/60). The MTD was further evaluated in phase II. RESULTS: Patients' characteristics were: 47 men, three women; median age 53 years (range 28-70); Zubrod performance status (PS) scores 0-1 (74%), PS 2 (26%); Okuda stage I (24%) and stage II (76%). Fifteen patients were enrolled in phase I: level 1 (n = 3), level 2 (n = 6), level 3 (n = 6), level 4 (n = 0). Level 2 was identified as the MTD. Dose-limiting toxicities included esophageal bleeding, grade 4 neutropenia and neutropenic fever. Of the 34 patients evaluable for response in phase II (of 35 total), there were four (11.8%) partial responses (95% CI, 0.8% to 22.8%) and six (17.6%) minor responses; nine (26.5%) had stable disease and 15 (44.1%) progressed. Sixteen per cent of patients had a decline of >or=50% in alpha-fetoprotein levels after treatment. Median survival and progression-free survival were 4.6 months (range 0.3-19.2) and 2.5 months (range 0.2-7.8), respectively, for 35 patients. Grade 3/4 hematological toxicities included anemia (45.7%), neutropenia (51.4%), thrombocytopenia (25.7%); febrile neutropenia (11.8%) and non-hematological toxicities were mild to moderate. CONCLUSIONS: Gemcitabine plus doxorubicin produces modest activity and moderate toxicity in this cohort of Chinese patients with advanced HCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Dose Máxima Tolerável , Invasividade Neoplásica/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biópsia por Agulha , Carcinoma Hepatocelular/mortalidade , Desoxicitidina/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Taiwan , Resultado do Tratamento , GencitabinaRESUMO
Telemedicine has been shown to have a considerable impact in medical education, conferencing and consultation. As a result, the People's Republic of China has been keen to develop telemedicine. In her attempts to further the development of telemedicine, China has looked to the progress of medical services in Western countries such as Europe and North America. The United States of America, however, has exceeded the rest in exchange of health-care information and telemedicine technologies with China. Although China has been enthusiastic about the exchange, telemedicine in China requires development in the technical infrastructure and professional infrastructure.
Assuntos
Telemedicina , China , Humanos , Cooperação Internacional , Desenvolvimento de Programas , Estados UnidosRESUMO
BACKGROUND: Cisplatin-based chemotherapy is the mainstay of the treatment for advanced urothelial cancer, but patients with renal insufficiency before therapy are usually contraindicated to receiving platinum-based chemotherapy. Paclitaxel is one of the most promising agents against advanced urothelial carcinoma in recent trials and it can be easily tolerated even in patients with compromised renal function. We conducted a study in order to evaluate the efficacy and safety of paclitaxel as a first-line therapy in advanced urothelial carcinoma patients. METHODS: Thirteen advanced chemo-naive urothelial carcinoma patients with a median age of 71 years were studied, seven of them demonstrating renal insufficiency (pretreatment serum creatinine > or = 1.5 mg/dl). All 13 patients received a minimum of two cycles of paclitaxel 175 mg/m2, delivered by intravenous infusion for 3 h every 3 weeks. RESULTS: Four of the 13 patients responded to treatment, a response rate of 30.8%, with two of these achieving complete remission and two showing partial responses. The median overall survival period of all 13 patients was nine months (95% Cl: 6.51-11.49) and our study revealed a statistical tendency in the difference of median overall survival time between responders and non-responders (13 months versus 7.5 months, log-rank p = 0.038), although the number of cases was limited. The differences in response rate and median overall survival time, comparing patients with renal insufficiency and those with normal renal function, were not significant. Treatment-related toxicity was mild, with only two (15.4%) patients suffering from grade 3-4 leukopenia. No treatment-related mortality was noted. CONCLUSIONS: Single-agent paclitaxel can be used as a first-line therapy in advanced urothelial carcinoma patients, and is especially suitable for those with pretreatment renal insufficiency, since the antitumor activity is significant while toxicity is well tolerated.
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Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Paclitaxel/administração & dosagem , Insuficiência Renal/complicações , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Neoplasias Ósseas/secundário , Carcinoma de Células de Transição/secundário , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Pelve Renal , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Tegafur-uracil has become an important regimen in the treatment of metastatic colorectal cancer. Tegafur is a prodrug that is converted to 5-fluorouracil (5-FU) and has been reported to be less toxic and to have a higher therapeutic index. The additional advantage of tegafur is oral administration, an important consideration to improve the quality of life in these patients. Tegafur in combination with uracil is thought to have greater anti-tumor activity due to the inhibitory effect of uracil on the degradation of 5-FU by hepatic dihydropyrimidine dehydrogenase. Tegafur with folinic acid has been reported with modest efficacy and acceptable toxicity. The purpose of this study was to evaluate the effectiveness and toxicity profile of oral tegafur-uracil plus folinic acid in Chinese patients with metastatic colorectal cancer. METHODS: Between May 1998 and August 1999, 40 patients with metastatic colorectal carcinoma were enrolled in this study. All the patients had to have measurable lesions. The initial dose of tegafur-uracil was 300 mg/m2/day for 28 days, followed by a 7-day rest period. Folinic acid was administered orally at a dose of 60 mg/day concurrently with tegafur-uracil. For patients with neutrophil count <1500/microl or a platelet count <100,000/microl after treatment, the treatment was postponed for a maximum of 2 weeks. After that time, if the neutrophil count was 1000-1500/microl and the platelet count was 70,000-100,000 microl, the dose of tegafur-uracil was reduced by 50%, and if lower values resulted, the treatment was discontinued. RESULTS: Forty patients received a total of 318 courses of treatment and a response rate of 32.5% (95% CI, 18-47%), including five complete remissions and eight partial remissions, was achieved. Toxicity was mild and generally tolerable. Gastrointestinal toxicities, including diarrhea, nausea and vomiting, were the major side effects. Seven incidences (17.5%) of grade 3-4 gastrointestinal toxicity were observed. Hematological toxicities were minimal with no evidence of severe (grade 3 or 4) leukopenia and thrombocytopenia. No episode of hepatic, renal, cardiac or neurological toxicity occurred. Two patients (5%) developed transient painful fissuring erythroderma over their palms and soles (the hand-foot syndrome). CONCLUSIONS: The data from our study indicate that oral tegafur-uracil plus folinic acid is an active and tolerable first-line treatment for Chinese patients with metastatic colorectal cancer, with the additional advantage of being easily administered at home.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Tegafur/administração & dosagem , Uracila/administração & dosagem , Vômito Precoce/etiologiaRESUMO
BACKGROUND: Bone marrow transplantation (BMT) is effective treatment for many hematologic disease, but performed in a population with a high endemic hepatitis B virus carrier rate, the incidence of liver function impairment and fulminant hepatitis (FH) is expected to be raised. METHODS: Forty-three hepatitis B virus carriers received high-dose chemotherapy and BMT, 32 patients received an allogeneic graft, and 11 patients autologous marrow. Acute graft-versus-host disease prophylaxis consisted of methotrexate on day 1, 3, 6, and 11 and cyclosporine for 6 months. RESULTS: After a median follow-up period of 68 months (range: 1-11.5 years), 26 (81.3%) allogeneic BMT patients developed impaired liver function (LF), 5 progressed to FH on day 93, 169, 170, 180, and 468, respectively, and died after an average of 13.8 days (range: 1-45 days). Whereas only 4 (36.4%) autologous BMT patients developed impaired LF, and none FH. Impaired LF (P=0.026, chi-square), and FH (odds ratio=12.86, P=0.009 for coefficient) were significantly related to an allogeneic marrow graft, and the timing of liver function impairment coincided with cyclosporine withdrawal. Hepatitis B surface antigen (HbsAg) disappeared from the serum in 4/14 (28.6%) patients receiving a marrow graft from an HbsAg+ donor. HbsAg was not detected in the serum after BMT in 2/11 (18.2%) autologous BMT patients. CONCLUSIONS: Hepatitis B virus carriers receiving a marrow graft from an HbsAg+ donor have a significantly increased risk of FH.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Portador Sadio/virologia , Hepatite B/transmissão , Hepatite/etiologia , Adolescente , Adulto , Alanina Transaminase/sangue , Análise de Variância , Anticorpos Antivirais/sangue , Portador Sadio/imunologia , Causas de Morte , Criança , Feminino , Hepacivirus/imunologia , Anticorpos Anti-Hepatite/sangue , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Testes de Função Hepática , Masculino , Análise de Sobrevida , Transplante Autólogo/efeitos adversos , Transplante Autólogo/mortalidade , Transplante Homólogo/mortalidadeRESUMO
BACKGROUND: Alterations of the p53 gene have been associated with the progression of certain human malignancies. To establish further the correlation between p53 gene alterations and progression of non-Hodgkin's lymphomas (NHLs), the authors analyzed both mutations and rearrangements of the p53 gene in a cohort of 84 NHLs. METHODS: Eighty-four NHLs were analyzed for p53 gene alterations. Point mutations of exons 5-9 were studied by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), and DNA rearrangements were studied by Southern blot analysis. RESULTS. Point mutations and DNA rearrangements of the p53 gene were detected in 6 (7.2%) and 3 (3.6%) patients, respectively. All p53 gene abnormalities were found exclusively in B-cell NHLs. Taken together, patients with p53 gene alterations had poorer survival than other patients (P = 0.024). However, of the three patients with p53 gene rearrangements, the two who appeared to have one normal allele showed a relatively better response to chemotherapy and had longer survival (27 and 47 months). In contrast, the remaining patient who had rearranged bands much stronger than the germline, and thus appeared to have both alleles rearranged, was refractory to chemotherapy and had poorer survival (6 months). CONCLUSIONS: Patients with NHLs of intermediate and high grades who carried point mutations or rearrangements of p53 genes had worse outcomes than other patients. Patients with one abnormal p53 allele and one residual normal allele had a more favorable prognosis than those with two abnormal alleles.
Assuntos
Rearranjo Gênico/genética , Genes p53/genética , Linfoma de Células B/genética , Linfoma não Hodgkin/genética , Mutação Puntual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Choque Cardiogênico/induzido quimicamente , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Colectomia , Esquema de Medicação , Eletrocardiografia , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Edema Pulmonar/induzido quimicamente , Choque Cardiogênico/diagnóstico , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgiaRESUMO
BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Viroses/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Portador Sadio/epidemiologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Humanos , Infusões Intravenosas , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/epidemiologia , Neoplasias Primárias Desconhecidas/virologia , Taiwan/epidemiologia , Trombocitopenia/induzido quimicamenteRESUMO
BACKGROUND: The efficacy of the treatment of advanced gastric cancer is not very good. The response rate to the original etoposide--leucovorin--5-fluorouracil (ELF) treatment is 53% with tolerable side effects. Whether increasing the dose intensity by prolonging the duration of infusion with 5-fluorouracil (5-FU) and leucovorin (LV) from 3 to 5 days for advanced or metastatic gastric cancer patients would enhance the efficacy but not increase side effects is still unknown. METHODS: Thirty-six advanced or metastatic gastric cancer and chemotherapy-naïve patients with measurable or evaluable diseases were scheduled to receive intravenous etoposide 100 mg/m2/day on days 2-4, LV 300 mg/m2/day intravenously and 5-FU 500 mg/m2/day intravenously on days 1-5, every 4 weeks. All patients who received at least two courses of chemotherapy were evaluated for tumor response, survival and response duration and toxicity according to the WHO criteria. RESULTS: Thirteen patients showed a response, including five with complete response (CR). The overall response rate was 36% (95% confidence interval, CI, 20-52%) in the whole group and 46% (95% CI 28-66%) in the 28 patients with measurable disease. The median progression-free interval and overall median survival time were 5 and 7 months, respectively. The most frequent toxicity was alopecia (grade I/II 56.3%). The incidence of grade III or greater myelosuppression was 5.9%. No treatment-related death occurred. CONCLUSIONS: The efficacy of the modified ELF by increasing the dosages of 5-FU and LV is not superior to the results of the original regimen, yet it is a relatively safe and tolerable combination regimen for advanced gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Alopecia/induzido quimicamente , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diarreia/induzido quimicamente , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucopenia/induzido quimicamente , Levoleucovorina , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade , Análise de SobrevidaRESUMO
The anti-emetic efficacy of a combination of tropisetron and dexamethasone was studied in 33 patients who underwent bone marrow transplantation. Another 50 patients receiving conventional anti-emetic therapies in bone marrow transplantation served as control. On the first and second days of preconditioning chemotherapy, 51% and 36% respectively of patients in the tropisetron and dexamethasone group did not experience vomiting, compared with only 12% and 10% of control group patients (P < 0.001). The mean number of episodes of vomiting in the tropisetron and dexamethasone group was also significantly lower than in the control group (0.97+/-1.65 vs 3.50+/-2.45 and 1.30+/-1.40 vs 4.44+/-2.91 respectively, both P < 0.001). Control of vomiting in the two groups was not significantly different during days 3-6. Analysis of patients receiving busulfan and cyclophosphamide as the preconditioning regimen still showed better anti-emetic control in the tropisetron and dexamethasone group than in the control group on the first two days of treatment (total control rate 33.3% vs 6.5% and 44.4% vs 12.9% respectively, P < 0.001). Patients given tropisetron and dexamethasone combination more frequently suffered from dizziness and burning sensation of the chest. However, diarrhea and extrapyramidal symptoms were the most frequent adverse effects seen after using conventional anti-emetic combination. The combination of tropisetron and dexamethasone was thus superior to conventional anti-emetic combinations in preventing vomiting during preconditioning period of bone marrow transplantation. The adverse effects of this combination were minimal and well tolerated by patients.
Assuntos
Antieméticos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea , Dexametasona/administração & dosagem , Indóis/administração & dosagem , Condicionamento Pré-Transplante , Vômito/prevenção & controle , Adolescente , Adulto , Antieméticos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/administração & dosagem , Carmustina/efeitos adversos , Criança , Ciclofosfamida/administração & dosagem , Citarabina/efeitos adversos , Dexametasona/efeitos adversos , Tontura/induzido quimicamente , Quimioterapia Combinada , Feminino , Cefaleia/induzido quimicamente , Azia/induzido quimicamente , Humanos , Indóis/efeitos adversos , Leucemia/tratamento farmacológico , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Podofilotoxina/efeitos adversos , Tropizetrona , Irradiação Corporal TotalRESUMO
A 22-year-old woman had a normal full-term delivery 6 years after a successful allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI) to a total of 1575 cGy in seven fractions (225 cGy x 7, at a dose rate of 3.5 cGy/min). Graft-versus-host disease prophylaxis was with methotrexate and cyclosporin A. Grade I acute GVHD developed after BMT but there was no chronic GVHD. She became amenorrhoeic after BMT and serial gonadal testing indicated hypergonadotrophic hypogonadism. She became pregnant and delivered a full-term, healthy baby 6 years after BMT. Successful pregnancy after TBI of more than 1200 cGy is extremely rare. This case, to the best of our knowledge, is the second patient who received a higher dose of TBI (1575 cGy) to have a successful pregnancy. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 1200 cGy.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/radioterapia , Leucemia Mieloide Aguda/terapia , Gravidez , Irradiação Corporal Total , Adulto , Amenorreia/etiologia , Antineoplásicos Alquilantes/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Recém-Nascido , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Ovário/efeitos da radiação , Dosagem Radioterapêutica , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversosRESUMO
Between January 1994 and November 1995, 41 patients with metastatic colorectal carcinoma were enrolled in this study. All these patients had recurrent disease after a prior 5-fluorouracil based adjuvant chemotherapy or failed to achieve response by prior chemotherapy that included 5-fluorouracil. 5-Fluorouracil, 2600 mg/m2, was administered concurrently with 100 mg/m2 leucovorin over 24 hours of continuous intravenous infusion. The treatment was repeated every week until progressive disease was documented. Forty-one patients received a total of 810 courses of treatment. The overall response rate was 17.1% (95% confidence interval 5.6-28.6%). In two patients who achieved complete response, the liver was the metastatic site. The median survival was 18.4 months for responders and 12.6 months for non-responders. Gastrointestinal toxicities including diarrhea, stomatitis, nausea and vomiting were the major side-effects. Sixteen incidences (39.0%) of grade 2-3 gastrointestinal toxicities were observed. One patient (2.4%) developed a grade 3 cardiac toxicity, and another one (2.4%) had a grade 2 neurotoxicity. Hematological toxicities were minimal with no evidence of severe (grade 2 or more) leukopenia or thrombocytopenia. We conclude that in patients with pretreated metastatic colorectal cancer, weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin is associated with higher efficacy and tolerable toxicity. This regimen is a good option as a second-line treatment for those whose diseases are recurrent from or refractory to prior 5-fluorouracil, and deserves a longer period of follow-up.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Neoplasias do Colo/patologia , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Análise de SobrevidaRESUMO
For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Cuidados Paliativos , Adulto , Idoso , Anemia/induzido quimicamente , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas/métodos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucopenia/induzido quimicamente , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Prognóstico , Análise de SobrevidaRESUMO
In a prospective phase II study, 102 women with advanced breast cancer were treated with low doses of cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) at weekly intervals by intravenous injection. Seventy-five patients were evaluable for treatment response and the overall response rate was 52% (95% confidence interval, 41-63%). Of the evaluable patients, 15% had complete response and 37% had partial response. The median survival after therapy was 15.6 months, the median time to progression was 6.8 months and the median duration of response was 9.1 months. The main toxicities were mild vomiting and moderate myelosuppression. There was only 1 patient who experienced heart failure. Weekly CAF appears to have an efficacy with tolerable side effects comparable to standard CAF with an every-3-week schedule.