RESUMEN
We performed a phase II study combining 41.8 degrees C whole body hyperthermia with ICE chemotherapy, i.e. ifosfamide (5 g/m(2)), carboplatin (300 mg/m(2)) and etoposide (150 mg/m(2) on days 2 and 3), administered every 4 weeks, for patients with malignant pleural mesothelioma. Of 27 chemonäive, non-metastatic patients enrolled, 25 patients were evaluable for response. Overall response rate was 20% (five partial remissions; 95% CI 8.9-39.1%). Median survival time from the start of treatment for all patients was 76.6 weeks (95% CI 65.4-87.8 weeks). Progression free survival for all patients measured 29.6 weeks (95% CI 24.4-34.7 weeks). One year overall survival was 68% and 2 year overall survival was 20%. Major treatment toxicities included grade 3/4 neutropenia and thrombocytopenia in 74 and 33% of treatment cycles, respectively. One patient died due to sepsis. These promising results are consistent with continued clinical investigation; a phase III clinical trial with whole body hyperthermia as the independent variable has been initiated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipertermia Inducida , Mesotelioma/tratamiento farmacológico , Mesotelioma/terapia , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/terapia , Anciano , Carboplatino , Terapia Combinada , Dexametasona , Supervivencia sin Enfermedad , Etopósido , Femenino , Humanos , Ifosfamida , Infusiones Intravenosas , Masculino , Mesotelioma/patología , Persona de Mediana Edad , Neoplasias Pleurales/patología , Sepsis/inducido químicamente , Resultado del TratamientoRESUMEN
Multiple myeloma is almost invariably fatal despite a wide variety of chemotherapeutic and supportive treatment options. There are several unresolved problems with existing approaches, including the specific indications for treatment; the optimal combination of agents and doses; and the type, frequency, and timing of high-dose therapy and stem-cell transplantation. High-dose chemotherapy followed by stem-cell transplantation produces higher remission rates, but patients rarely, if ever, are cured by a single regimen. Allogeneic hematopoietic stem-cell transplantations offer a potential graft-versus-myeloma (GVM) effect. Researchers are focusing efforts on improving the safety of transplant procedures, increasing response rates to ablative therapy, and testing novel posttransplant options to improve outcomes. The newly devised National Comprehensive Cancer Network (NCCN) guidelines for treating multiple myeloma are also discussed.
Asunto(s)
Mieloma Múltiple/terapia , Humanos , Mieloma Múltiple/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Trasplante Autólogo , Trasplante HomólogoRESUMEN
The overall goal of adoptive immunotherapy with genetically modified lymphocytes is to decrease the morbidity and mortality associated with allogeneic bone marrow transplantation. The initial data reviewed here suggest that the behavior of the allogeneic HStk transgenic cells can be modified after administration to patients. Further study is needed to identify the response rates and risks associated with this procedure. In particular, larger studies will be needed with appropriate randomization to determine if the response rate to genetically modified cells is equivalent to the response rates with unmodified cells. Wider application of these techniques in the initial setting of allogeneic transplantation will undoubtedly occur and such trials have been initiated at several institutions. Careful attention to vector, suicide gene, selectable marker, efficiency of transduction, and cell dose will be necessary when comparing different trials since these variables will probably affect transgenic cell survival and response rates. [figure: see text]