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1.
J Bone Oncol ; 10: 49-56, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29577024

RESUMO

Background: Bone metastases and lytic lesions due to multiple myeloma are common in advanced cancer and can lead to debilitating complications (skeletal-related events [SREs]), including requirement for radiation to bone. Despite the high frequency of radiation to bone in patients with metastatic bone disease, our knowledge of associated healthcare resource utilization (HRU) is limited. Methods: This retrospective study estimated HRU following radiation to bone in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and Switzerland. Eligible patients were ≥ 20 years old, had bone metastases secondary to breast, lung or prostate cancer, or bone lesions associated with multiple myeloma, and had received radiation to bone between 1 July 2004 and 1 July 2009. HRU data were extracted from hospital patient charts from 3.5 months before the index SRE (radiation to bone preceded by a SRE-free period of ≥ 6.5 months) until 3 months after the last SRE that the patient experienced during the study period. Results: In total, 482 patients were included. The number of inpatient stays increased from baseline by a mean of 0.52 (standard deviation [SD] 1.17) stays per radiation to bone event and the duration of stays increased by a mean of 7.8 (SD 14.8) days. Outpatient visits increased by a mean of 4.24 (SD 6.57) visits and procedures by a mean of 8.51 (SD 7.46) procedures. Conclusion: HRU increased following radiation to bone across all countries studied. Agents that prevent severe pain and delay the need for radiation have the potential to reduce the burden imposed on healthcare resources and patients.

2.
Crit Rev Oncol Hematol ; 115: 67-80, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28602171

RESUMO

A systematic literature review was conducted to quantify populations of patients with primary breast cancer in whom bone metastases were detected at study start or during follow-up. Searches were performed in PubMed and EMBASE using terms related to breast cancer and bone metastases. Articles had to have been published 01/01/99-31/12/13, and to report data on the proportion of patients with bone metastases among patients with breast cancer. In total, 156 articles were included in the meta-analysis. A median of 12% of patients with stage I-III breast cancer developed bone metastases during a median follow-up of 60 months. Of patients who developed metastatic disease during follow-up, 55% (median) had bone metastases. Of those with metastatic breast cancer at study start, 58% (median) had bone metastases. These data help to inform on the global burden of bone metastases by defining patient populations that are at risk of developing bone metastases.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Neoplasias Ósseas/epidemiologia , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Estadiamento de Neoplasias
3.
J Bone Oncol ; 5(4): 185-193, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28008381

RESUMO

BACKGROUND: Skeletal-related events (SREs; pathologic fracture [PF], spinal cord compression and radiation or surgery to bone) are common complications of bone metastases or bone lesions and can impose a considerable burden on patients and healthcare systems. In this study, the healthcare resource utilisation (HRU) associated with PFs in patients with bone metastases or lesions secondary to solid tumours or multiple myeloma was estimated in eight European countries. METHODS: Eligible patients were identified in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and Switzerland. HRU data were extracted from hospital charts from 3.5 months before the index PF (defined as a PF preceded by a 6.5-month period without a SRE) until 3 months after the last SRE during the study period. Changes from baseline in the number and duration of inpatient stays, number of outpatient visits and number of procedures provided were recorded. RESULTS: Overall, 118 patients with PFs of long bones (those longer than they are wide, e.g. the femur) and 241 patients with PFs of other bones were included. Overall, HRU was greater in patients with long bone PFs than in those with PFs of other bones. A higher proportion of patients with long bone PFs had multiple SREs (79.7%), and more of their SREs were considered to be linked (73.4%) compared with patients with PFs of other bones (51.0% and 47.2%, respectively). CONCLUSION: The increased number and duration of inpatient stays for PFs of long bones compared with those for PFs of other bones may be due in part to the requirement for complicated and lengthy rehabilitation in patients with long bone PFs. Implementing strategies to delay or reduce the number of PFs experienced by patients with bone metastases or lesions may therefore reduce the associated HRU and patient burden.

4.
Pharmacoepidemiol Drug Saf ; 25(3): 238-50, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26521865

RESUMO

BACKGROUND: The PROTECT Benefit-Risk group is dedicated to research in methods for continuous benefit-risk monitoring of medicines, including the presentation of the results, with a particular emphasis on graphical methods. METHODS: A comprehensive review was performed to identify visuals used for medical risk and benefit-risk communication. The identified visual displays were grouped into visual types, and each visual type was appraised based on five criteria: intended audience, intended message, knowledge required to understand the visual, unintentional messages that may be derived from the visual and missing information that may be needed to understand the visual. RESULTS: Sixty-six examples of visual formats were identified from the literature and classified into 14 visual types. We found that there is not one single visual format that is consistently superior to others for the communication of benefit-risk information. In addition, we found that most of the drawbacks found in the visual formats could be considered general to visual communication, although some appear more relevant to specific formats and should be considered when creating visuals for different audiences depending on the exact message to be communicated. CONCLUSION: We have arrived at recommendations for the use of visual displays for benefit-risk communication. The recommendation refers to the creation of visuals. We outline four criteria to determine audience-visual compatibility and consider these to be a key task in creating any visual. Next we propose specific visual formats of interest, to be explored further for their ability to address nine different types of benefit-risk analysis information.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Apresentação de Dados , Farmacoepidemiologia/métodos , Medição de Risco/métodos , Sistemas de Notificação de Reações Adversas a Medicamentos/instrumentação , Comunicação , Tomada de Decisões , Farmacoepidemiologia/instrumentação
5.
Lancet ; 386(9992): 433-43, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26040499

RESUMO

BACKGROUND: Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. METHODS: In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. INTERPRETATION: Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. FUNDING: Amgen.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/complicações , Fraturas Ósseas , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Áustria , Densidade Óssea/fisiologia , Neoplasias da Mama/tratamento farmacológico , Denosumab , Método Duplo-Cego , Feminino , Fraturas Ósseas/complicações , Fraturas Ósseas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Suécia , Resultado do Tratamento
6.
Am J Clin Oncol ; 31(1): 49-54, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18376228

RESUMO

OBJECTIVE: We report a single-institution Phase I or II trial of surgical debulking, intraperitoneal chemotherapy, and immunotherapy followed by whole abdominal radiotherapy in patients with malignant peritoneal mesothelioma. METHODS: Between 1997 and 2000, 27 patients with malignant peritoneal mesothelioma were enrolled: 23 with epithelial subtype and 4 with sarcomatoid or mixed subtype. The treatment regimen consisted of surgical debulking followed by 4 intraperitoneal courses of cisplatin alternating with 4 courses of doxorubicin, 4 doses of intraperitoneal gamma interferon, a second laparotomy with resection of residual disease plus intraoperative intraperitoneal mitomycin and cisplatin heated to 41 degrees C, and finally whole abdominal radiotherapy. RESULTS: The median overall survival was 70 months with a 3-year survival of 67% (95% confidence interval, 46%-81%). Fourteen patients have died of their disease with a median time to death of 17 months (range, 0.4-71 months) after consenting to treatment. Seven patients are alive without evidence of disease with a median follow-up of 90 months (range, 71-110 months), and 6 are alive with disease with a median follow-up of 86 months (range, 70-106 months). The regimen was well tolerated. There were no patients with Grade III or IV hematological toxicities, 2 patients with Grade III ototoxicity, and 3 patients with Grade III gastrointestinal toxicity. CONCLUSION: Based on the results of this study, intensive multimodality therapy appears feasible and effective in this group of patients.


Assuntos
Neoplasias Abdominais/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Mesotelioma/terapia , Neoplasias Peritoneais/terapia , Adulto , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Doxorrubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/radioterapia , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/radioterapia , Neoplasias Peritoneais/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
7.
Cancer ; 98(9): 1942-6, 2003 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-14584078

RESUMO

BACKGROUND: The objective of this study was to assess the efficacy and toxicity of the imidazotetrazine derivative temozolomide for patients with unresectable or metastatic soft tissue sarcoma. METHODS: Twenty-five of 26 patients were eligible and assessable for toxicity and response. Temozolomide was administered twice daily on a 12-hour schedule for 5 days as an oral bolus dose of 200 mg/m(2) followed by 9 doses of 90 mg/m(2) every 4 weeks. RESULTS: There were 2 partial responses, 2 mixed responses, and 3 patients with stable disease that lasted > 6 months, for an overall objective response rate of 8%. At a median follow-up of 13.2 months, the median progression-free survival and the median overall survival were 2.0 months (95% confidence interval [95% CI], 1.7-2.3) and 13.2 months (95% CI, 4.7-31.1), respectively. All responding patients had leiomyosarcoma of uterine or nonuterine origin; and, in a subset analysis of these patients, the objective response rate was 18% (2 of 11 patients), with disease stabilization occurring in 3 of 11 patients (27%). For this subgroup, at a median follow-up of 24.4 months, the median progression-free survival and the median overall survival were 3.9 months (95% CI, 1.9-21.9) and 30.8 months (lower-bound 95% CI, 7.8), respectively. There were no treatment-related deaths or National Cancer Institute Grade 4 toxicities. Grade 3 toxicities included nausea, anemia, fatigue, elevated alkaline phosphatase levels and nonneutropenic fever (1 patient each). CONCLUSIONS: Temozolomide at the dose schedule employed in the current study was tolerated well and had modest activity against previously treated unresectable or metastatic leiomyosarcoma of both uterine and nonuterine origin.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/toxicidade , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Feminino , Humanos , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoma/secundário , Temozolomida , Resultado do Tratamento , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/secundário
8.
Cancer Immun ; 3: 13, 2003 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-14533943

RESUMO

The efficacy of current standard therapies for the treatment of sarcoma remains limited. With the aim of identifying target antigens relevant to the development of vaccine-based immunotherapy of sarcoma, we have addressed the relevance of tumor-specific antigens encoded by genes belonging to the SSX family as vaccine targets in sarcoma tumors. Expression of SSX-1 to -5 was analyzed in a collection of sarcoma tumors of diverse histological subtypes and in sarcoma cell lines. We found expression of at least one SSX-encoded antigen in 42% of sarcoma tumors, including 5 of 7 different histological subtypes, and in 50% of sarcoma cell lines. SSX-1 was the most frequently expressed family member, followed by SSX-4, -2 and -5. Expression of SSX-3 was detected in only one sample. Importantly, most SSX positive samples co-expressed more than one family member. In addition, assessment of CD8+ T cell recognition of HLA-A2+ SSX-2+ sarcoma cells showed that the latter were efficiently recognized and lysed by SSX-2-specific CTLs. The results of this study indicate that SSX antigens are relevant targets for the development of vaccine-based immunotherapy of sarcoma and encourage the start of vaccination trials using SSX-derived immunogens in sarcoma patients.


Assuntos
Antígenos de Neoplasias/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Proteínas de Neoplasias/uso terapêutico , Proteínas Repressoras/uso terapêutico , Sarcoma/imunologia , Humanos , Sarcoma/patologia , Células Tumorais Cultivadas , Vacinas Sintéticas/uso terapêutico
9.
Cancer ; 98(2): 331-6, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12872353

RESUMO

BACKGROUND: The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte-colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma. METHODS: Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m2 over 3 hours (total dose of 14 g/m2), plus mesna at a dose of 0.56 g/m2 prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 microg/kg/day was administered subcutaneously on days 6-15. RESULTS: Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0-14%) and 1 was an unconfirmed response (3%; 95% CI, 5-14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3-7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6-9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure. CONCLUSIONS: This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Ifosfamida/uso terapêutico , Mesna/uso terapêutico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Masculino , Mesna/administração & dosagem , Mesna/efeitos adversos , Pessoa de Meia-Idade , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/efeitos adversos , Proteínas Recombinantes , Resultado do Tratamento
10.
Leuk Lymphoma ; 44(3): 477-81, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12688318

RESUMO

As both fludarabine and rituximab are active against indolent lymphoproliferative disorders, we have studied the combination of fludarabine and rituximab in patients with low-grade lymphoma and chronic lymphocytic leukemia (CLL) in phase I/II fashion. Of 33 patients enrolled, 21(63.6%) had low-grade lymphoma and 12 (36.4%) had CLL. They received fludarabine 30 mg/m2 on days 1-4 and rituximab 125, 250 or 375 mg/m2 on day 5 at intervals of 28 days to a maximum of 8 cycles. Three patients were removed from the study because of rituximab-associated anaphylaxis and four because of prolonged hematopoietic toxicity. Toxicity and responsiveness did not differ at the different dose levels of rituximab. For 29 evaluable patients, responses were seen in 82.8% and complete responses in 34.5%. Of 7 responding patients not referred for stem cell transplantation, 6 remain in complete remission at a median follow-up of 16 months (range 4-30 months). Of 13 previously untreated patients, all responded and 46.2% had a complete response. Of 16 previously treated patients, 68.5% responded and 25% had a complete response. The combination of fludarabine and rituximab has major activity and acceptable toxicity in patients with low-grade lymphoma and CLL.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma não Hodgkin/terapia , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anafilaxia/etiologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Antimetabólitos Antineoplásicos/efeitos adversos , Terapia Combinada , Feminino , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Indução de Remissão , Rituximab , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos
11.
Cancer ; 97(3): 537-44, 2003 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-12548594

RESUMO

BACKGROUND: The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P-glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over-express P-glycoprotein. To further evaluate the combinations clinical efficacy and safety, a trial was performed in heavily pretreated patients with metastatic breast carcinoma (MBC). METHODS: Thirty-six patients with MBC were treated with estramustine 900 mg/m(2) per day divided into 3 doses given on Days 1-3 and docetaxel 70 mg/m(2) given by intravenous administration over 1 hour on Day 3 after the first dose of estramustine, every 21 days. Patients may have received any number of prior chemotherapy regimens for MBC. RESULTS: Nine partial responses were observed in 31 assessable patients, for an objective response rate of 29% (95% confidence interval, 14-48%). The median progression free survival was 4 months (range, 1-41 months), and the median overall survival was 17 months (range, 2-45 months). Severe toxicities (Grade 3 or 4) were neutropenia, hypophosphatemia, and thrombosis. Seventy-five percent of patients experienced either an improvement or no change in quality of life. CONCLUSIONS: The combination of docetaxel and estramustine produced responses in heavily pretreated women with MBC while maintaining quality of life.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Docetaxel , Estramustina/administração & dosagem , Estramustina/efeitos adversos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Qualidade de Vida , Indução de Remissão , Análise de Sobrevida
12.
J Clin Invest ; 110(12): 1813-22, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12488431

RESUMO

The cancer-testis antigen NY-ESO-1 is one of the most promising candidates for generic vaccination of cancer patients. Here we analyzed the CD8(+) T cell response to a NY-ESO-1 peptide vaccine composed of the two previously defined peptides 157-165 and 157-167, administered with GM-CSF as a systemic adjuvant. The NY-ESO-1 peptide vaccine elicited a CD8(+) T cell response directed against multiple distinct epitopes in the 157-167 region, as revealed by using A2/peptide multimers incorporating overlapping A2 binding peptides in this region. However, only a minor fraction of the elicited CD8(+) T cells, namely those recognizing the peptide 157-165 with sufficiently high functional avidity, recognized the naturally processed target on NY-ESO-1(+) tumor cells. In contrast, the majority of peptide 157-165-specific CD8(+) T cells exhibited lower functional avidity and no tumor reactivity. In addition, vaccine-elicited CD8(+) T cells specific for other overlapping epitopes in the 157-167 region failed to significantly recognize NY-ESO-1-expressing tumor targets. Thus, because of the complexity of the CD8(+) T cell repertoire that can be elicited by vaccination with synthetic peptides, a precise definition of the targeted epitope, and hence, of the corresponding peptide to be used as immunogen, is required to ensure a precise tumor targeting.


Assuntos
Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Epitopos/metabolismo , Proteínas de Membrana , Neoplasias/imunologia , Proteínas/imunologia , Vacinas de Subunidades/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/metabolismo , Células Cultivadas , Epitopos/imunologia , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Humanos , Leiomiossarcoma/imunologia , Leiomiossarcoma/terapia , Masculino , Neoplasias/terapia , Ligação Proteica , Sarcoma Sinovial/imunologia , Sarcoma Sinovial/terapia , Vacinas de Subunidades/uso terapêutico
13.
J Thorac Cardiovasc Surg ; 124(6): 1145-8, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12447180

RESUMO

OBJECTIVE: The prognosis for patients with primary cardiac sarcoma is poor. Median survival is less than 10 months, especially when complete surgical excision is not feasible. Removal of all cardiopulmonary structures involved by tumor followed by orthotopic allotransplantation has been proposed to improve long-term survival. METHODS: From 1996 through 1999, we performed combined heart and lung resection followed by en bloc heart and bilateral lung transplantation in 4 patients (2 men and 2 women): 2 with inoperable pulmonary arterial sarcoma and 2 with left atrial sarcoma extending into the pulmonary vein. RESULTS: Median age at diagnosis was 39 years (range 37-45 years). All 4 patients were given chemotherapy before transplantation: doxorubicin and ifosfamide in 2 cases, and doxorubicin, ifosfamide, mesna, and dacarbazine in 2 cases. There were no operative deaths. Median survival after transplantation was 31 months (range 5-49 months). All patients had tumor recurrence: local recurrence in the chest (n = 1) and distant metastases in the brain (n = 2) and abdomen (n = 1). One patient remains alive 49 months after disease progression with cerebral metastasis as the only site of recurrence treated with whole-brain irradiation, resection, and stereotactic radiosurgery. CONCLUSIONS: Combined heart and lung transplantation is a technically feasible treatment for highly selected patients with localized advanced primary cardiac sarcomas. The high incidence of metastatic disease, however, limits its utility.


Assuntos
Neoplasias Cardíacas/cirurgia , Transplante de Coração-Pulmão , Sarcoma/cirurgia , Adulto , Antineoplásicos/uso terapêutico , Feminino , Neoplasias Cardíacas/tratamento farmacológico , Neoplasias Cardíacas/mortalidade , Humanos , Masculino , Recidiva Local de Neoplasia , Artéria Pulmonar , Sarcoma/tratamento farmacológico , Sarcoma/mortalidade , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/mortalidade , Neoplasias Vasculares/cirurgia
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