RESUMO
BACKGROUND & AIMS: The CpG island methylator phenotype (CIMP), defined by a high frequency of aberrantly methylated genes, is a characteristic of a subclass of colon tumors with distinct clinical and molecular features. Cohort studies have produced conflicting results on responses of CIMP-positive tumors to chemotherapy. We assessed the association between tumor CIMP status and survival of patients receiving adjuvant fluorouracil and leucovorin alone or with irinotecan (IFL). METHODS: We analyzed data from patients with stage III colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL after surgery, from April 1999 through April 2001. The primary end point of the trial was overall survival and the secondary end point was disease-free survival. DNA isolated from available tumor samples (n = 615) was used to determine CIMP status based on methylation patterns at the CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1 loci. The effects of CIMP on survival were modeled using Kaplan-Meier and Cox proportional hazards; interactions with treatment and BRAF, KRAS, and mismatch repair (MMR) status were also investigated. RESULTS: Of the tumor samples characterized for CIMP status, 145 were CIMP positive (23%). Patients with CIMP-positive tumors had shorter overall survival times than patients with CIMP-negative tumors (hazard ratio = 1.36; 95% confidence interval: 1.01-1.84). Treatment with IFL showed a trend toward increased overall survival for patients with CIMP-positive tumors, compared with treatment with fluorouracil and leucovorin (hazard ratio = 0.62; 95% CI: 0.37-1.05; P = .07), but not for patients with CIMP-negative tumors (hazard ratio = 1.38; 95% CI: 1.00-1.89; P = .049). In a 3-way interaction analysis, patients with CIMP-positive, MMR-intact tumors benefited most from the addition of irinotecan to fluorouracil and leucovorin therapy (for the interaction, P = .01). CIMP was more strongly associated with response to IFL than MMR status. Results for disease-free survival times were comparable among all analyses. CONCLUSIONS: Patients with stage III, CIMP-positive, MMR-intact colon tumors have longer survival times when irinotecan is added to combination therapy with fluorouracil and leucovorin.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Ilhas de CpG , Metilação de DNA , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Quimioterapia Adjuvante , Colectomia , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Reparo de Erro de Pareamento de DNA , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Evaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients' diagnoses were essential thrombocythemia (ET n = 146), polycythemia vera (PV n = 120), primary myelofibrosis (n = 12), and unclassifiable MPN (MPNu n = 5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p = 0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p = 0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.
Assuntos
Povo Asiático/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/genética , Doenças Vasculares/etiologia , Doenças Vasculares/genética , Idoso , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Hemorragia/genética , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Mutação , Trombose/epidemiologia , Trombose/etiologia , Trombose/genética , Doenças Vasculares/epidemiologiaRESUMO
PURPOSE: To evaluate if raising baseline and maintaining hemoglobin (Hb) levels with red blood cell (RBC) transfusion could improve the outcomes of chemotherapy for advanced gastric cancer (AGC). METHODS: Patients were randomized to receive RBC transfusion to maintain their Hb levels >or=10 g/dl (arm 1) or >or=12 (arm 2) before the start of their 5-fluorouracil-based first-line chemotherapy. Objective response, KPS and quality of life (QOL) data were measured. RESULTS: For 87 patients enrolled, mean baseline Hb was 10.1 g/dl, and 54 patients received RBC prior to chemotherapy initiation. Despite transfusion, we failed to maintain the Hb level above the predefined target range. Eighteen patients experienced brief and reversible adverse events during transfusion, including two patients with acute pulmonary edema. KPS was improved from baseline to post-chemotherapy in both arms. QOL data showed improvement in some symptom scores, but there was no difference in the QOL scores between the two arms at baseline and all four cycles of treatment. Similar response rates were observed in both arms (arm 1, 30%; arm 2, 35%). Both arms showed similar chemotherapy duration (3.8 and 4.1 months, respectively), progression-free survival (4.0 and 4.1 months) and overall survival (9.9 and 9.3 months). CONCLUSIONS: Red blood cell transfusion achieving Hb level above 10 g/dl might contribute to the improvement of the KPS and QOL seen in patients with AGC. The observation of equivalent outcomes at the two target Hb levels supports the feasibility of anemia correction to Hb 10 g/dl, which merits further evaluation.
Assuntos
Anemia/sangue , Anemia/tratamento farmacológico , Antimetabólitos Antineoplásicos/efeitos adversos , Transfusão de Eritrócitos , Fluoruracila/efeitos adversos , Hemoglobinas/metabolismo , Neoplasias Gástricas/complicações , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Contagem de Células Sanguíneas , Determinação de Ponto Final , Transfusão de Eritrócitos/efeitos adversos , Feminino , Fluoruracila/uso terapêutico , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Qualidade de Vida , Neoplasias Gástricas/tratamento farmacológico , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the efficacy of intravenous lorazepam as premedication for bone marrow aspiration and biopsy (BMAB). DESIGN: Randomized, double-blind, placebo-controlled. PATIENTS: One hundred and thirty-eight consenting patients planned to receive BMAB. INTERVENTION: Patients were randomly assigned to receive either intravenous lorazepam 1 mg or placebo just prior to BMAB. SETTING: Tertiary referral center, inpatient setting. OUTCOME MEASURES: A questionnaire was used to determine the patient perception about the procedure and pain at baseline, which was completed just after the procedure, and the next day after the BMAB. Pain was rated using a 10-cm linear visual analog scale (VAS). RESULTS: The mean VAS scores measured during the BMAB examination were 6.0 for lorazepam vs 6.2 for placebo. Few adverse events were noted during intravenous lorazepam administration. The patients in the lorazepam group were more likely to accept the next BMAB (P = 0.044). CONCLUSION: Intravenous lorazepam was safe in patients undergoing BMAB and was more effective than placebo in enhancing cooperation during BMAB and willingness to undergo another procedure. However, use of lorazepam 1 mg provided no reduction in the pain associated with BMAB. Further studies should focus on providing appropriate analgesia for this potentially painful procedure.
Assuntos
Ansiolíticos/uso terapêutico , Biópsia por Agulha/efeitos adversos , Medula Óssea/patologia , Hipnóticos e Sedativos/uso terapêutico , Lorazepam/uso terapêutico , Dor/prevenção & controle , Adolescente , Adulto , Idoso , Ansiolíticos/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Injeções Intravenosas , Lorazepam/administração & dosagem , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Placebos , Inquéritos e QuestionáriosRESUMO
Imatinib mesylate is the first molecule of targeted therapy in chronic myelogenous leukaemia inhibiting constitutively activated BCR-ABL kinase. There are no long-term follow-up studies of large sample sizes to assess the toxicity of the use of imatinib mesylate over 10 years. Several cases of hepatotoxicity, including fatal liver failure, have been associated with the long-term use of imatinib mesylate. We report here on a patient who experienced immediate dominant cholestatic damage of the liver and mild hepatocyte damage during imatinib mesylate therapy. This differs from most reports showing dominantly acute hepatitis with necrosis associated with the use of imatinib mesylate.
Assuntos
Antineoplásicos/efeitos adversos , Crise Blástica/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase Intra-Hepática/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas , Ductos Biliares/patologia , Citarabina/administração & dosagem , Toxidermias/etiologia , Hepatócitos/patologia , Humanos , Idarubicina/administração & dosagem , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêuticoRESUMO
BACKGROUND: Mapping of brain perfusion using bolus tracking methods is increasingly used to assess the amount and severity of cerebral ischemia in acute stroke. Using relative perfusion maps, however, it is difficult to identify the tissue at risk-maximum (TARM) of infarction with sufficient reliability and reproducibility. METHODS: We analysed 76 perfusion computed tomography (PCT) derived maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) in 40 acute stroke patients using multidetector row technology and standard software (Somatom VolumeZoom, Siemens, Germany). 'Window narrowing' of the color maps was performed until color homogenisation of the contralateral unaffected hemisphere was reached. Tissue still depictable on the affected hemisphere after sufficient window narrowing was defined as the TARM. We analysed presence and size of the TARM on PCT maps, its relative perfusion values by comparison with contralateral, mirrored tissue, and its correlation with occurrence and final size of cerebral infarction on follow-up imaging. RESULTS: An ischemic area was visible in 64, 58.9 and 72.6% on the conventional CBF, CBV and TTP maps, respectively. After window narrowing, a TARM was present in 56.8, 54.1 and 63.0% of slices comprising 11.9, 11.6 and 21.1% of the ipsilateral hemisphere (CBF, CBV and TTP), respectively. The relative perfusion values were 38.7 (CBF) and 43.0% (CBV) for the entire ischemic area and 11.3 (CBF) and 13.3% (CBV) for the TARM. Definite cerebral infarction was visible on 68.1% of the target slices comprising 23.7 +/- 22.9% of the ipsilateral hemisphere. The size of the TARM correlated slightly better with the final infarction size (r=0.74-0.82) than the entire ischemic area (r=0.61-0.79). With respect to the occurrence of cerebral infarction, the presence of a TARM on CBF maps showed the best positive (97.9%) and negative (72.7%) predictability. DISCUSSION: On PCT maps, window narrowing provides a standardized display of the TARM in peracute stroke. The severely reduced values of relative CBF and CBV suggest the TARM to indicate tissue most prone to infarction.
Assuntos
Mapeamento Encefálico , Circulação Cerebrovascular , Perfusão , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Tomografia Computadorizada por Raios X/normas , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: Nail toxicity is one of the most frequent non-hematologic toxicities of docetaxel and often deteriorates patients' quality of life, leading to treatment discontinuation. To define the incidence of nail change as well as its association with specific risk factors, we prospectively investigated data of 84 consecutive patients with advanced non-small cell lung cancer who received first-line docetaxel/cisplatin combination chemotherapy. METHODS: Chemotherapy-naïve patients were treated with docetaxel, either 3-weekly or weekly, in combination with cisplatin. All patients received adequate premedications including corticosteroids, antiemetics and intravenous hydration. Toxicity was evaluated using National Cancer Institute (NCI) CTCAE version 3. RESULTS: Twenty-two patients (26%) developed nail changes, including nine (11%) with grade 3. Nine patients who developed grade 3 nail changes (seven of whom received weekly docetaxel) were not able to complete planned chemotherapy despite topical and/or oral antibiotic treatment. Most occurrences of nail changes were diagnosed in patients who were treated with weekly schedule (P = 0.02). The number of chemotherapy cycles and cumulative docetaxel doses were strongly associated with the development of nail changes. The cumulative hazard of developing nail changes increased above 10% after 2.8 months up to 40% at 6 months. A multivariate analysis of factors associated with the development of nail changes identified the following to have independent adverse significance: weekly docetaxel administration (odds ratio, 0.084; 95% CI, 0.014-0.510; P = 0.01) and the number of chemotherapy cycles given (odds ratio, 0.232; 95% CI, 0.067-0.805; P = 0.02). CONCLUSION: Nail changes occur with more frequent and prolonged use of docetaxel.
Assuntos
Antineoplásicos/toxicidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Taxoides/toxicidade , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Docetaxel , Esquema de Medicação , Humanos , Estudos Prospectivos , Taxoides/administração & dosagemRESUMO
AIMS AND BACKGROUND: The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor and shares intrinsic tyrosine kinase activity. The phosphatase and tensin homolog mutated on chromosome ten (PTEN) gene product is a protein tyrosine phosphatase that participates in modulating the phosphoinositide 3-kinase pathway which has antagonizing activity to protein tyrosine kinase. The authors investigated the correlation between clinicopathologic variables including survival and the overexpression of the p185(HER2) with loss of PTEN expression in gastric adenocarcinoma patients. METHODS: The protein expression of p185(HER2) and PTEN was examined by immunohistochemical stain in paraffin-embedded tissues of 94 (M:F, 52:42) gastric adenocarcinoma patients by using monoclonal antibody, and the results were related to clinicopathological variables and survival. RESULTS: p185(HER2) overexpression correlated positively with lymph node metastasis, distant metastasis, AJCC classification, higher relapse rate. Patients with overexpression of p185(HER2) were found to have significantly lower disease-free survival (P = 0.003) and overall survival (P = 0.0004). Loss of PTEN expression correlated positively with depth of invasion (T stage) and was more frequent in the advanced stage. The patient group with p185(HER2) overexpression and loss of PTEN expression showed significantly shorter disease-free and overall survival (P = 0.03, P = 0.01) than the other groups. CONCLUSIONS: Our observations suggest potential prognostic significance of p185(HER2) overexpression with PTEN loss in gastric adenocarcinoma patients. This opens up the possibility of considering p185(HER2)and PTEN as a therapeutic target in gastric cancer.
Assuntos
Adenocarcinoma/química , Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , PTEN Fosfo-Hidrolase/análise , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Regulação para Baixo , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/enzimologia , Análise de Sobrevida , Regulação para CimaRESUMO
BACKGROUND AND PURPOSE: With new CT technologies, including CT angiography (CTA), perfusion CT (PCT), and multidetector row technique, this method has regained interest for use in acute stroke assessment. We have developed a score system based on Multimodal Stroke Assessment Using CT (MOSAIC), which was evaluated in this prospective study. METHODS: Forty-four acute stroke patients (mean age, 63.8 years) were enrolled within a mean of 3.0+/-1.9 hours after symptom onset. The MOSAIC score (0 to 8 points) was generated by results of the 3 sequential CT investigations: (1) presence and amount of early signs of infarction on noncontrast CT (NCCT; 0 to 2 points), (2) stenosis (>50%) or occlusion of the distal internal carotid or middle cerebral artery on CTA (0 to 2 points), and (3) presence and amount of reduced cerebral blood flow on 2 adjacent PCT slices (0 to 4 points). The predictive value of the MOSAIC score was compared with each single CT component with respect to the final size of infarction and the clinical outcome 3 months after stroke by use of the modified Rankin Scale (mRS) and the Barthel Index (BI). RESULTS: Among the CT components, PCT showed the best correlation to infarction size (r=0.75) and clinical outcome (r=0.60 to 0.62) compared with NCCT (r=0.43 to 0.58) and CTA (r=0.47 to 0.71). The MOSAIC score showed consistently higher correlation factors (r=0.67 to 0.78) and higher predictive values (0.73 to 1.0) than all single CT components with respect to outcome measures. A MOSAIC score <4 predicted independence with 89% to 96% likelihood (mRS =2, BI >/=90); a MOSAIC score <5 predicted fair outcome with 96% to 100% likelihood (mRS =3, BI >/=60). CONCLUSIONS: The MOSAIC score based on multidetector row CT technology is superior to NCCT, CTA, and PCT in predicting infarction size and clinical outcome in hyperacute stroke.
Assuntos
Infarto Cerebral/diagnóstico , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Tomografia Computadorizada por Raios X , Doença Aguda , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/terapia , Meios de Contraste/administração & dosagem , Feminino , Seguimentos , Heparina/uso terapêutico , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Taxa de Sobrevida , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Clinically silent circulating microembolic signals (MES) can be identified by transcranial Doppler ultrasound (TCD). It is not yet clear whether their occurrence is always linked to the presence of embolic sources. METHODS: 24 terminally ill patients (7 women, 17 men; mean age 68 years) were investigated by TCD of the middle cerebral arteries. These findings were correlated with a complete post-mortem examination of potential embolic pathways. RESULTS: Four patients out of the 24 under investigation showed MES, 2 of them bilaterally. All these 4 MES-positive patients had a definite embolic source, i. e. bilateral carotid artery occlusive disease, endocarditis with thrombotic valvular adhesions and severe plaques in the aortic arch, dilated left atrium and a patent foramen ovale, or severe plaques in the aortic arch and a dilated left atrium, respectively. CONCLUSION: In the investigated patient group, we could demonstrate that MES can only be found when an embolic source is present. The finding of MES justifies an extensive clinical and laboratory search for potential embolic sources including extracranial and intracranial colour-coded duplex ultrasound, ECG, Holter-ECG, and TEE.
Assuntos
Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia Doppler Transcraniana/métodosRESUMO
Carotid bruits are supposed to indicate the presence of high-grade common carotid or extracranial internal carotid artery stenosis in a large proportion of patients. Using a stethoscope, we prospectively auscultated 273 carotid arteries of 145 patients blinded to the results of a complete extracranial and intracranial Doppler investigation including extracranial color-coded duplex ultrasound. Fifty-four arteries showed stenosis of > or = 50%-99%, or occlusion of the extracranial internal or the common carotid artery. In 25 of these arteries, a bruit was present. In 9 out of 16 patients with extracranial stenosis from 70%-99%, a bruit was detected. In one additional patient with a middle-grade external carotid artery stenosis, a bruit was also present. In seven additional patients, a bruit was present in the absence of any carotid artery stenosis, cardiac vitium or goiter. The sensitivity of carotid auscultation for the detection of a 70%-99% stenosis of the common or extracranial internal carotid artery was 56% and specificity was 91%. The positive predictive value of a bruit found during carotid auscultation was 27%, and the negative predictive value of a normal auscultation was 97%. Carotid auscultation is a useful screening procedure in the detection of carotid stenosis or occlusion, but requires confirmation by carotid ultrasound.
Assuntos
Auscultação/estatística & dados numéricos , Estenose das Carótidas/diagnóstico por imagem , Ultrassonografia Doppler Dupla/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Auscultação/normas , Auscultação/tendências , Estenose das Carótidas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Ultrassonografia Doppler Dupla/normasRESUMO
A phase II study was performed to evaluate the clinical efficacy and toxicity of oxaliplatin combined with uracil and tegafur (UFT) in patients with advanced colorectal cancer previously treated with a fluoropyrimidine-based regimen. From January to December 1999, 34 patients were enrolled in this study. Patients received intravenous oxaliplatin 130 mg/m2 on day 1 and daily oral UFT 350 mg/m2 in 3 divided doses for 21 days and repeated every 21 days. Thirty-one of 34 patients were assessable for response and 32 patients for toxicity. Partial response was observed in four patients and stable disease in six patients. The response rate was 12.9% (95% CI, 3.6-29.8%) and median duration of response was 17 weeks. The median overall survival and progression-free survival of all patients were 26 weeks (range, 3-90+ weeks) and 9 weeks (range, 3-56 weeks), respectively. Sensory neuropathy was the most common toxicity, but there was no severe toxicity (>grade II) except for a case of grade III neutropenia. We conclude that oxaliplatin and UFT combination chemotherapy was well tolerated without significant toxicities. The results of this trial will serve as the basis for designing new clinical trials with a different dose or schedule.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Análise de Sobrevida , Tegafur/administração & dosagem , Uracila/administração & dosagemRESUMO
PURPOSE: When designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons. PATIENTS AND METHODS: Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC-either docetaxel 60 mg/m(2) every 3 weeks or irinotecan 150 mg/m(2) every 2 weeks-was left to the discretion of investigators. Primary end point was overall survival (OS). RESULTS: Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116). CONCLUSION: To our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Terapia de Salvação , Neoplasias Gástricas/terapia , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Terapia Combinada , Docetaxel , Feminino , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos de Platina/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Prospectivos , Pirimidinas/administração & dosagem , República da Coreia , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/mortalidade , Taxoides/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To determine whether patients' self-reported quality-of-life (QOL) parameters could predict survival for patients with advanced gastric cancer (AGC) treated with first-line chemotherapy, we performed this analysis based on the data obtained from 254 patients enrolled in three consecutive prospective randomized trials at a single institution. METHODS: Consenting patients with AGC received first-line chemotherapy as specified in the protocols. QOL was assessed at baseline using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires. Baseline univariate and multivariate analyses were performed on the QOL data and the recognized clinical predictors for survival. RESULTS: Of 254 patients, 164 completed the QOL questionnaire at baseline. All patients received fluorouracil-containing first-line chemotherapy for AGC. With 88% observed deaths and a reported median survival of 9.5 months [95% confidence interval (CI) 8.8-10.2 months], there were no significant differences in survival between patients with or without QOL data. The final Cox multivariate model revealed four prognostic factors: age [hazard ratio (HR) 2.08, 95% CI 1.32-3.33, P = 0.002], bone metastasis (HR 2.70, 95% CI 1.30-5.56, P = 0.008), hemoglobin (HR 0.58, 95% CI 0.37-0.92, P = 0.020), and social functioning (HR 0.40, 95% CI 0.23-0.64, P = 0.001). When adjusting for clinical parameters, social functioning was an independently significant prognostic factor for longer survival. CONCLUSION: Baseline social functioning, along with age, presence of bone metastasis, and baseline hemoglobin level, independently predicts survival of AGC patients treated with first-line chemotherapy. QOL assessment should be routinely included to provide useful prognostic information concerning AGC patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Qualidade de Vida , Autoimagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Adulto , Fatores Etários , Idoso , Neoplasias Ósseas/secundário , Estudos de Coortes , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Apoio Social , Neoplasias Gástricas/psicologia , Análise de SobrevidaRESUMO
S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anemia Hemolítica/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Combinação de Medicamentos , Fadiga/induzido quimicamente , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Metástase Neoplásica , Ácido Oxônico/administração & dosagem , Taxa de Sobrevida , Tegafur/administração & dosagem , Resultado do TratamentoRESUMO
Neurofibromatosis type 1 (von Recklinghausen's disease, NF-1) is an autosomal-dominant neurocutaneous disorder characterized by abnormal skin pigmentation (café au lait spots and axillary freckling), cutaneous and plexiform neurofibromas, skeletal dysplasias, and Lisch nodules (pigmented iris hamartomas). Gastrointestinal stromal tumors (GISTs) are the most common tumors of mesenchymal origin in the gastrointestinal tract, mesentery, omentum, and retroperitoneum. Here, we report a case of GIST in the ileum of a 76-year-old woman previously diagnosed as NF-1. She was admitted due to sudden onset of abdominal pain. Contrast enhanced CT scan revealed a moderately defined, peripherally enhanced soft tissue mass of about 8.8 x 7.3cm, originating from the small bowel in the left of the abdomen. Surgical excision was performed and the tumor was found to be composed of tumor cells that were positive for c-kit protein. The patient started imatinib treatment a month later, but stopped medication due to dyspepsia after a few months and eventually progressed after 18 months.
Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico , Neurofibromatose 1/diagnóstico , Dor Abdominal , Idoso , Feminino , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Neurofibromatose 1/patologia , Neurofibromatose 1/cirurgia , Fatores de RiscoRESUMO
Intestinal marginal zone B-cell lymphoma of the MALT type (I-MZL) is a relatively uncommon form of lymphoma. Twenty-seven patients with histologically-confirmed I-MZL were analyzed. The patients initially presented with abdominal pain (62.9%), and diarrhea (22.2%). The most common involved site was the ileo-caecal area (40.7%). Musshoff's stage I(E), II(E)1, II(E)2, III(E) and IV were present in 44%, 15%, 11%, 7.4% and 22% respectively. Sixty-three percent were in the low-risk group according to the Follicular Lymphoma International Prognostic Index. Complete response and partial response were achieved in 82% and 4% patients. The estimated 5-year overall survival (OS) and progression-free survival (PFS) rates were 86% and 54%. Stage > or = II(E)2 was determined to be a poor prognostic factor for PFS and OS. I-MZL commonly manifests in an early-stage, low-risk state and tends to respond well to local and systemic treatment with favorable prognosis. I-MZL tends to be an indolent disease - characterized by prolonged survival with frequent relapses, similarly to other site MZLs.
Assuntos
Neoplasias do Ceco/mortalidade , Neoplasias do Íleo/mortalidade , Linfoma de Zona Marginal Tipo Células B/mortalidade , Doenças Raras/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ceco/diagnóstico , Neoplasias do Ceco/patologia , Neoplasias do Ceco/terapia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias do Íleo/diagnóstico , Neoplasias do Íleo/patologia , Neoplasias do Íleo/terapia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Doenças Raras/diagnóstico , Doenças Raras/patologia , Doenças Raras/terapia , Recidiva , Fatores de Risco , Taxa de SobrevidaRESUMO
PURPOSE: Irinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study. MATERIALS AND METHODS: Chemotherapy-naive AGC patients received irinotecan 150 mg/m(2) on day 1, and leucovorin 200 mg/m(2) and a 22-h infusion of FU 1000 mg/m(2) on days 1 and 2. Cisplatin 30 mg/m(2) was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity. RESULTS: Of the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response. CONCLUSION: This novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.
RESUMO
BACKGROUND: Thalidomide has been reported to have antitumor activity for treating metastatic hepatocellular carcinoma (HCC). We evaluated the safety and efficacy of using thalidomide for treating selected patients with unresectable or metastatic HCC, and their disease was refractory to systemic chemotherapy. METHODS: Eight patients with measurable and metastatic HCC that had progressed with prior systemic chemotherapy and who desired further active therapy were enrolled in this study. Thalidomide was given orally at bedtime and it was started at 200 mg/day with no further dose escalation. The response was measured at 2-month intervals. RESULTS: The median age was 44 years (range: 34-52 years) and all the patients had received doxorubicin-based systemic chemotherapy prior to their enrollment. Each patient received thalidomide for a median of 152 days (range: 5-422 days). One partial response was observed (12.5%, 95% CI; 0-42%) along with 4 cases of stable diseases. The most commonly encountered toxicity was somnolence; grade 3 somnolence was noted for one patient, which led to treatment discontinuation. Skin rash was observed in one responding patient. CONCLUSIONS: The results indicate that thalidomide may feasibly offer disease stabilization to metastatic HCC patients. Further dose escalation of thalidomide, or its combination with other chemotherapeutic agents, may be of interest and this should be investigated for treating patients with metastatic HCC.
Assuntos
Neoplasias Ósseas/secundário , Carcinoma Hepatocelular/tratamento farmacológico , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/secundário , Talidomida/uso terapêutico , Adulto , Neoplasias Ósseas/tratamento farmacológico , Carcinoma Hepatocelular/secundário , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Nodal marginal zone B-cell lymphoma (NMZL) is a relatively uncommon type of lymphoma. Because of the rarity, the natural history and the optimal treatment modality have not been well defined. Therefore, we performed a retrospective analysis of the clinical features and treatment outcomes of NMZL. Thirty-six patients who were histologically diagnosed as NMZL were included in the analysis. Fifty-three percent of the patients had localized disease (stages I and II), and 21.2% (7/33) had bone marrow involvement at presentation. B symptom was present in only three patients (8.3%). Most patients were categorized as low or low-intermediate risk group by international prognostic index (IPI) (77.1%). Majority (94.4%) of the patients with localized disease achieved complete remission (CR) after the initial treatment. Of the seven patients with disseminated disease, who were treated with anthracycline-based chemotherapy, four patients achieved CR. Of the seven patients who received nonanthracycline-based chemotherapy, no patient achieved CR. After the median follow-up duration of 36 months, the median progression-free survival (PFS) was 3.9 (95% CI; 2.9-5.6) years, and the estimated 5-year PFS and overall survival rates were 47.2 and 82.7%, respectively. The significant predictive factors for PFS were performance status, advanced stage, and follicular lymphoma IPI (FLIPI) in this study. This clinical feature is similar to FL rather than to MZL-MALT type.