Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Oncologist ; 17(12): 1541-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22622148

RESUMO

PURPOSE: To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer. PATIENTS AND METHODS: In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed. RESULTS: All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m2 given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD. CONCLUSION: Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Doxorrubicina/análogos & derivados , Neoplasias Bucais/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/efeitos adversos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Diagnóstico Bucal/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/patologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Polietilenoglicóis/administração & dosagem , Fatores de Risco
2.
Clin Cancer Res ; 27(13): 3556-3566, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33820780

RESUMO

PURPOSE: Leucine-rich repeat containing 15 (LRRC15) is expressed on stromal fibroblasts in the tumor microenvironment of multiple solid tumor types and may represent an interesting target for therapy, particularly in patients with sarcomas where LRRC15 is also expressed by malignant cells. ABBV-085 is a monomethyl auristatin-E antibody-drug conjugate that targets LRRC15 and showed antineoplastic efficacy in preclinical experiments. Herein, we report findings of ABBV-085 monotherapy or combination therapy in adult patients with sarcomas and other advanced solid tumors. PATIENTS AND METHODS: This first-in-human phase I study (NCT02565758) assessed ABBV-085 safety, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity. The study consisted of two parts: dose escalation and dose expansion. ABBV-085 was administered by intravenous infusion at 0.3 to 6.0 mg/kg every 14 days. RESULTS: In total, 85 patients were enrolled; 45 patients received the recommended expansion dose of 3.6 mg/kg ABBV-085 monotherapy, including 10 with osteosarcoma and 10 with undifferentiated pleomorphic sarcoma (UPS). Most common treatment-related adverse events were fatigue, nausea, and decreased appetite. The overall response rate for patients with osteosarcoma/UPS treated at 3.6 mg/kg was 20%, including four confirmed partial responses. No monotherapy responses were observed for other advanced cancers treated at 3.6 mg/kg. One patient treated with ABBV-085 plus gemcitabine achieved partial response. CONCLUSIONS: ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Imunoconjugados , Neoplasias , Sarcoma , Adulto , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Humanos , Imunoconjugados/efeitos adversos , Proteínas de Membrana/genética , Neoplasias/patologia , Sarcoma/tratamento farmacológico , Sarcoma/genética , Microambiente Tumoral
3.
Leuk Res ; 32(5): 823-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17915315

RESUMO

Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia rarely occur concurrently. We report a case in which these disorders were associated with an occult large granular lymphocyte leukemia. The peripheral blood cytopenias improved after glucocorticoids and intravenous immunoglobulin were administered, and response was maintained with cyclosporine. Large granular lymphocyte leukemia should be suspected in the setting of unexplained bone marrow failure.


Assuntos
Leucemia Linfocítica Granular Grande/complicações , Púrpura Trombocitopênica/complicações , Aplasia Pura de Série Vermelha/complicações , Adulto , Antígenos CD/análise , Feminino , Humanos , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Leucemia Linfocítica Granular Grande/imunologia , Receptores Imunológicos/análise , Família de Moléculas de Sinalização da Ativação Linfocitária
4.
Clin Cancer Res ; 24(12): 2749-2757, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29559563

RESUMO

Purpose: This first-in-human study aimed to determine the MTD and safety of MEDI3617, a selective anti-angiopoietin-2 (Ang2) mAb, alone and combined with bevacizumab or cytotoxic chemotherapy.Patients and Methods: This phase I/Ib, multicenter, open-label, dose-escalation and dose-expansion study evaluated patients with advanced solid tumors. Patients received intravenous MEDI3617 as monotherapy [5-1,500 mg every 3 weeks (Q3W)] or with bevacizumab every 2 weeks (Q2W) or Q3W, weekly paclitaxel, or carboplatin plus paclitaxel Q3W. Dose expansions included a monotherapy cohort in platinum-resistant ovarian cancer and a bevacizumab combination cohort in bevacizumab-refractory malignant glioma. Safety/tolerability, pharmacokinetics, pharmacodynamics, and clinical activity were assessed.Results: We enrolled 116 patients. No formal MTD was identified (monotherapy or combination therapy). MEDI3617 demonstrated linear pharmacokinetics and maximal accumulation of peripheral Ang2 binding at doses above 300 mg Q3W. MEDI3617 monotherapy safety profile was acceptable, except in advanced ovarian cancer [prolonged grade 3 edema-associated adverse events (AE) occurred]. Otherwise, MEDI3617 combined with chemotherapy or bevacizumab was well tolerated. The AE profiles of MEDI3617 and bevacizumab were largely non-overlapping. Overall response rates in ovarian cancer and glioma monotherapy dose-expansion arms were 6% and 0%, respectively.Conclusions: Recommended MEDI3617 monotherapy dosage is 1,500 mg Q3W or 1,000 mg Q2W, except in ovarian cancer. Although peripheral edema has occurred with other Ang2 inhibitors, the severity and duration seen here in ovarian cancer potentially identifies a new, clinically significant safety signal for this class of agents. On the basis of limited clinical activity, MEDI3617 development was discontinued. Clin Cancer Res; 24(12); 2749-57. ©2018 AACR.


Assuntos
Angiopoietina-2/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/mortalidade , Paclitaxel/administração & dosagem , Resultado do Tratamento , Adulto Jovem
5.
Catheter Cardiovasc Interv ; 66(3): 424-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16208708

RESUMO

A 38-year-old man with a history of migraine headaches with aura and one episode of ischemic stroke was found to have a patent foramen ovale (PFO). After percutaneous closure with the nickel-containing Amplatzer PFO occluder, the patient developed pericarditis, atrial fibrillation, and increased migraine headaches with aura that abated with oral prednisone. He tested positive for nickel hypersensitivity, which we conclude is the likely etiology of his pericarditis.


Assuntos
Procedimentos Cirúrgicos Cardíacos/instrumentação , Comunicação Interatrial/cirurgia , Hipersensibilidade/complicações , Níquel/efeitos adversos , Pericardite/etiologia , Próteses e Implantes/efeitos adversos , Implantação de Prótese/instrumentação , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia Transesofagiana , Glucocorticoides/uso terapêutico , Humanos , Masculino , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/etiologia , Pericardite/diagnóstico por imagem , Pericardite/tratamento farmacológico , Prednisolona/uso terapêutico , Implantação de Prótese/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA