RESUMO
Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Imunoterapia/métodos , Quimioterapia de Indução/métodos , Acetilcisteína/administração & dosagem , Acetilcisteína/efeitos adversos , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/uso terapêutico , Carcinoma/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Celecoxib , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Imunização , Estimativa de Kaplan-Meier , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversosRESUMO
PURPOSE: It has been reported that insulin increases the cytotoxic effect in vitro of methotrexate by as much as 10,000-fold. The purpose of this study was to explore the clinical value of insulin as a potentiator of methotrexate. PATIENTS AND METHODS: Included in this prospective, randomized clinical trial were 30 women with metastatic breast cancer resistant to fluorouracil + Adriamycin + cyclophosphamide and also resistant to hormone therapy with measurable lesions. Three groups each of ten patients received two 21-day courses of the following treatments: insulin + methotrexate, methotrexate, and insulin, respectively. In each patient, the size of the target tumor was measured before and after treatment according to the Response Evaluation Criteria In Solid Tumors. The changes in the size of the target tumor in the three groups were compared statistically. RESULTS: Under the trial conditions, the methotrexate-treated group and the insulin-treated group responded most frequently with progressive disease. The group treated with insulin + methotrexate responded most frequently with stable disease. The median increase in tumor size was significantly lower with insulin + methotrexate than with each drug used separately. DISCUSSION: Our results confirmed in vivo the results of previous in vitro studies showing clinical evidence that insulin potentiates methotrexate under conditions where insulin alone does not promote an increase in tumor growth. Therefore, the chemotherapy antitumoral activity must have been enhanced by the biochemical events elicited in tumor cells by insulin. CONCLUSIONS: In multidrug-resistant metastatic breast cancer, methotrexate + insulin produced a significant antitumoral response that was not seen with either methotrexate or insulin used separately.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Insulina/uso terapêutico , Metotrexato/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/toxicidade , Neoplasias da Mama/patologia , Divisão Celular , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Insulina/toxicidade , Metotrexato/toxicidade , Pessoa de Meia-IdadeRESUMO
Lately, the promising results obtained with autologous cancer vaccines are stimulating new research in the old field of cancer immunotherapy. This paper describes the development of a procedure previously reported by us that is used to obtain an autologous hemoderivative with antitumoral properties. The procedure has been tested in a phase I-II, randomized, controlled clinical trial of 28 cancer patients with different primary malignancies in metastatic and chemotherapy-resistant stages. The histology of the lesions that responded to this treatment was consistent with the characteristic histology observed in malignant lesions treated with a similar antitumoral hemoderivative: proliferation of stromal connective tissue, T-lymphocyte infiltration, and a reduction in the amount of tumor cells and blood vessels. We concluded that vaccination had elicited an immune response because a delayed-type hypersensitivity test made with the autologous hemoderivative produced a significantly more intense response in the responding treated patients. We propose that an immune mechanism acting on tumor cells and/or the regulatory system for stromal growth explains the histological results observed. The use of blood to obtain the immunogen allows vaccination to be repeated, so this method could avoid tumor escape responses due to mutations in the antigen library of the tumor. The results of our study justify further research to optimize the antitumoral effect of vaccination.
Assuntos
Antígenos de Neoplasias/imunologia , Autoantígenos/imunologia , Vacinas Anticâncer/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Neoplasias/terapia , Células Estromais/patologia , Idoso , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Hipersensibilidade Tardia/etiologia , Imunoterapia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/prevenção & controle , Metástase Neoplásica/terapia , Neoplasias/imunologia , Neoplasias/patologia , Células Estromais/metabolismo , Transplante Autólogo , Vacinação/métodosRESUMO
Con el objetivo de integrar el diagnóstico virológico a la práctica clínica y de valorar los aspectos clínico radiológicos y evolutivos se llevó a cabo en el Servicio Pediátrico C del Hospital Pereira Rossell durante los meses de mayo a setiembre del año 1997 un estudio unicéntrico y prospectivo durante el cual ingresaron 56 pacientes menores de 24 meses procedentes de Montevideo y del interior del país. En todos se realizó aspirado nasofaríngeo para diagnóstico virológico por inmunofluorescencia indirecta, así como valoración de los diferentes aspectos clínicos y radiológicos. De los resultados obtenidos se destacan: predominio de edad menor de 1 año y del grupo menor de 3 meses, procedencia mayoritaria de Montevideo, de medio deficitario. Predominaron los niños bien nutridos sin antecedentes patológicos. Los síntomas predominantes fueron la polipnea, tos y tirajes, el aspecto radiológico, la hiperinsuflación aislada o asociada a procesos inhomogéneos difusos uni o bilaterales. Se obtuvo un elevado número de positivos para detección virológica (64,4 por ciento) con predominancia de virus sincicial respiratorio. En general hubo una evolución satisfactoria y se destaca un importante número de niños tratados con antibióticos. Se jerarquiza el trabajo en equipo como experiencia enriquecedora del grupo y la importancia de contar con el diagnóstico virológico como herramienta de trabajo en la clínica
Assuntos
Humanos , Lactente , Infecções Respiratórias/etiologia , Infecções Respiratórias/virologia , Técnica Indireta de Fluorescência para AnticorpoRESUMO
Con el objetivo de integrar el diagnóstico virológico a la práctica clínica y de valorar los aspectos clínico radiológicos y evolutivos se llevó a cabo en el Servicio Pediátrico C del Hospital Pereira Rossell durante los meses de mayo a setiembre del año 1997 un estudio unicéntrico y prospectivo durante el cual ingresaron 56 pacientes menores de 24 meses procedentes de Montevideo y del interior del país. En todos se realizó aspirado nasofaríngeo para diagnóstico virológico por inmunofluorescencia indirecta, así como valoración de los diferentes aspectos clínicos y radiológicos. De los resultados obtenidos se destacan: predominio de edad menor de 1 año y del grupo menor de 3 meses, procedencia mayoritaria de Montevideo, de medio deficitario. Predominaron los niños bien nutridos sin antecedentes patológicos. Los síntomas predominantes fueron la polipnea, tos y tirajes, el aspecto radiológico, la hiperinsuflación aislada o asociada a procesos inhomogéneos difusos uni o bilaterales. Se obtuvo un elevado número de positivos para detección virológica (64,4 por ciento) con predominancia de virus sincicial respiratorio. En general hubo una evolución satisfactoria y se destaca un importante número de niños tratados con antibióticos. Se jerarquiza el trabajo en equipo como experiencia enriquecedora del grupo y la importancia de contar con el diagnóstico virológico como herramienta de trabajo en la clínica(AU)