Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cancer Sci ; 108(11): 2213-2220, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28837250

RESUMO

This phase 1, open-label, dose-escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg b.i.d. on days 1-21 with carboplatin (area under the concentration-time curve 6 mg/mL•min) on day 1 and paclitaxel 80 mg/m2 on days 1, 8 and 15 every 3 weeks for up to 6 21-day cycles. Dose escalation followed a 3 + 3 design to determine dose-limiting toxicities, maximum tolerated dose and the recommended phase 2 dose. Nine patients (median age 62 [range 27-72] years) received a median of 5 (range 3-6) cycles of treatment (3 at 100 mg, 6 at 150 mg). There were no dose-limiting toxicities. The most common adverse events of any grade were neutropenia (100%), alopecia (89%), peripheral sensory neuropathy (78%), and anemia, nausea and malaise (67% each). Grade 3 or 4 adverse events were associated with myelosuppression. Pharmacokinetics of carboplatin/paclitaxel were similar at both veliparib doses. Response, assessed in five patients, was partial in four and complete in one (objective response rate 100%). The response could not be assessed in four patients who had no measurable disease at baseline. The recommended phase 2 dose of veliparib, when combined with carboplatin/paclitaxel, is 150 mg b.i.d. Findings from this phase 1 trial demonstrate the tolerability and safety of veliparib with carboplatin/paclitaxel, a regimen with potential clinical benefit in Japanese women with ovarian cancer.


Assuntos
Benzimidazóis/administração & dosagem , Carboplatina/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Carboplatina/efeitos adversos , Carboplatina/farmacocinética , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética
2.
Ann Nucl Med ; 29(7): 643-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25921216

RESUMO

OBJECTIVE: Multidrug resistance (MDR) has been suggested to be a major cause of failure of chemotherapy treatment for cancer. It is associated with the expression of MDR-related and apoptosis-related proteins. Recently, technetium-99m hexakis 2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR. The aim of this study was to evaluate (99m)Tc-MIBI single-photon emission computed tomography (SPECT)(/CT) for functional imaging of MDR-related and apoptosis-related proteins in patients with ovarian cancer. METHODS: Eleven women (mean age 63 years, range 53-76) with a clinical suspicion of ovarian cancer were prospectively studied. All patients were examined with (99m)Tc-MIBI imaging before surgery. After intravenous injection of 740 MBq (99m)Tc-MIBI, SPECT(/CT) imaging at 10 min and 2 h was performed. Based on the semiquantitative analysis of (99m)Tc-MIBI SPECT(/CT), both early and delayed tumor uptake ratios and washout rate % were calculated. The expression of MDR-related and apoptosis-related proteins was assessed in surgically excised tumors. Immunohistochemical staining was performed to quantify the expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein1 (MRP1), MRP3, lung resistance protein (LRP), breast cancer resistance protein (BCRP), Y-box-binding protein-1 (YB-1), Bcl-2, Bax and glutathione-S-transferase. (99m)Tc-MIBI imaging results and immunohistochemical results were compared. RESULTS: Laparotomy was performed in all patients. Six ovarian cancers were proven by histopathological examination. Five of the six ovarian cancers were positive for (99m)Tc-MIBI uptake on both early and delayed images with (99m)Tc-MIBI SPECT(/CT). MDR-related and apoptosis-related proteins were found to be expressed in all tumors. For the five positive (99m)Tc-MIBI uptake cases, the washout rate % of (99m)Tc-MIBI uptake showed a significant positive correlation with the expression of YB-1 (r = 0.988, P = 0.0015), and the early tumor uptake ratio showed a significant positive correlation with the expression of Bax (r = 0.882, P = 0.047). CONCLUSIONS: Our results suggested that (99m)Tc-MIBI SPECT(/CT) might be a valuable diagnostic imaging technique to evaluate MDR-associated YB-1 and Bax-mediated apoptosis in patients with ovarian cancer.


Assuntos
Apoptose , Resistência a Múltiplos Medicamentos , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/diagnóstico , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Multimodal , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia
3.
Cancer Sci ; 104(10): 1285-94, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23829867

RESUMO

Refractory bone and soft tissue sarcomas are challenging diseases to treat because of their robustness to chemotherapy. Although cancer vaccines have the potential to become an attractive treatment modality, their progress has been hampered by the presence of many subtypes of sarcomas and different human leukocyte antigen (HLA)-types. We investigated whether personalized peptide vaccination (PPV) would be feasible for the vast majority of sarcoma patients. Twenty refractory bone and soft tissue sarcoma patients with nine different subtypes and 11 different HLA-class IA phenotypes were enrolled in this study. A maximum of four HLA-matched peptides showing higher peptide-specific IgG responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the HLA-A2, -A3, -A11, -A24, -A26, -A31, and -A33 types, and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific CTL and IgG responses along with other laboratory analyses were conducted before and after vaccination. No patients were excluded by either sarcoma subtypes or different HLA-types. No severe adverse events associated with PPV were observed in any patients. Peptide-specific immunological boosting was observed in the post-vaccination samples from the majority of patients. Tumor reduction of the lung metastasis and a long stable disease was observed in each case, and the median overall survival time of the 20 cases was 9.6 months. Taken together, PPV could be feasible for the vast majority of refractory sarcoma patients because of the safety and higher rates of immunological responses regardless of the presence of different sarcoma subtypes and various HLA-types.


Assuntos
Neoplasias Ósseas/terapia , Vacinas Anticâncer/uso terapêutico , Imunoterapia Ativa , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Adulto , Idoso , Antígenos de Neoplasias/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/imunologia , Vacinas Anticâncer/efeitos adversos , Terapia Combinada , Citocinas/sangue , Feminino , Gastroenteropatias/induzido quimicamente , Antígenos HLA/análise , Doenças Hematológicas/induzido quimicamente , Humanos , Imunoglobulina G/sangue , Imunoterapia Ativa/efeitos adversos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Medicina de Precisão , Terapia de Salvação , Sarcoma/tratamento farmacológico , Sarcoma/imunologia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/imunologia , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento , Vacinação , Vacinas de Subunidades Antigênicas/efeitos adversos , Vacinas de Subunidades Antigênicas/uso terapêutico , Adulto Jovem
4.
Oncol Rep ; 25(1): 57-62, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21109957

RESUMO

The purpose of this study was to investigate severe adverse events (SAEs) after therapeutic peptide vaccination for advanced cancer patients. We investigated SAEs following personalized peptide vaccinations in 500 advanced cancer patients, including 174 prostate, 74 colon, 51 pancreatic and 43 gastric cancer patients. The number of vaccination cycles varied widely, from 3 to 112. The severity of adverse events was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3, and events with a grade of >3 were defined as SAEs and were evaluated by the Institutional Safety Evaluation Committee. A total of 215 SAEs in 102 patients were recorded during the vaccine trials. The main causes for these events were cancer progression (152 SAEs in 78 patients), combined cancer treatments other than vaccination (35 in 21 patients), diseases other than cancer (20 in 19 patients), peptide vaccines (6 in 6 patients) and suicide (1 in 1 patient). The 6 vaccine-related SAEs, all grade 3, consisted of skin reactions at each injection site, cellulitis around the injection site, edemas of the head and neck regions, colitis, rectal bleeding and bladder-vaginal fistulae. Both cellular and humoral responses to the vaccinated peptides were highly boosted in all 6 of these patients, indicating the involvement of augmented immune responses in these SAEs. The clinical responses in these 6 patients consisted of 2 partial responses and 4 stable diseases. The majority of SAEs after peptide vaccination for advanced cancer patients were caused by cancer progression. The appearance of vaccine-related SAEs, except inflammatory injection site reactions, was unexpected, and fortunately the incidence was very low. Our results suggest that physicians should be on guard for these rare SAEs associated with augmented immune responses.


Assuntos
Vacinas Anticâncer/efeitos adversos , Neoplasias/terapia , Vacinação/efeitos adversos , Idoso , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Vacinas de Subunidades Antigênicas/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...