RESUMEN
In a phase II trial we tried to evaluate the efficacy of a sequential combination of high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (ADM). In a pilot study we had found high-dose MTX effective as a single agent in gastric cancer. MTX and 5-FU were combined sequentially because Cadman et al had shown synergism for this combination. The therapy protocol consisted of high-dose MTX, 1.5 g/m2 of body surface, and high-dose 5-FU, 1.5 g/m2. MTX was administered 1 hr prior to 5-FU. Both drugs were given as a bolus. Twenty-four hours after MTX administration, citrovorum factor rescue was started, 15 mg/m2, q.6h. X 12, orally. Forty-eight hours after MTX administration, serum concentration of the drug was measured by high performance liquid chromatography (HPLC). Fourteen days after MTX was given, ADM, 30 mg/m2, was injected as a bolus. This protocol was repeated every 28 days. Patients eligible for this treatment should have a creatinine clearance of greater than 60 ml/min. The study included 30 patients with metastasizing gastric cancer and performance status between 40% and 70%. The response rate was 63% (19 of 30 patients). Two of 30 patients had complete remissions, which are still maintained. The median survival for responders is not yet evaluable: 68% are living after 17+ mo. The median survival for nonresponders was only 5 mo. The difference in survival curves is significant at a level of p less than 0.05. Cytostatic treatment was well tolerated. Fifty percent of the patients could be treated on an outpatient basis. Total alopecia was observed in only 10% of the patients. Severe leukopenia, thrombocytopenia, and kidney disorders were not observed.
Asunto(s)
Doxorrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Metotrexato/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Atención Ambulatoria , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Probabilidad , Neoplasias Gástricas/cirugía , Factores de TiempoRESUMEN
The possible effectiveness of methotrexate, 5-fluorouracil and adriamycin was tested in a phase I/II study of patients with metastasising gastric carcinoma. complete of partial remission occurred in 19 of 30 patients (approximately 63%). Two of 30 patients had complete remission. Median survival time of patients with remission cannot as yet be determined: about 68% are still alive after 17 months. Median survival time of patients with advanced tumour was only five months. The difference in survival curve is statistically significant (P less than 0.05). The study is continuing.
Asunto(s)
Doxorrubicina/uso terapéutico , Fluorouracilo/uso terapéutico , Metotrexato/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Doxorrubicina/administración & dosificación , Quimioterapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Neoplasias Gástricas/patologíaAsunto(s)
Fluorouracilo/análogos & derivados , Neoplasias Gastrointestinales/tratamiento farmacológico , Tegafur/uso terapéutico , Animales , Carcinoma de Ehrlich/tratamiento farmacológico , Quimioterapia Combinada , Masculino , Ratones , Metástasis de la Neoplasia , Tegafur/administración & dosificaciónRESUMEN
Bone marrow from 52 healthy donors has been fractionated on two discontinuous albumin gradients with different osmolarities in an effort to eliminate immunocompetent cells and to isolate hemopoietic stem cells. The nutrient agar system of Robinson was utilised as an assay procedure for the detection of colony-forming cells (CFU-c) in the resulting fractions. CFU-c, early granulocytic progenitors, are consistently present in the lighter fractions. On cytochemical staining, they showed a positive reaction for enzymes bound to lysosomes. The concentration of CFU-c was in an average 7 times that of the original marrow. At best, 1 X 10(5) CFU-c could be isolated from 10 ml marrow corresponding to 2 X 10(8) buffy-coat cells. The presence of immunocompetent cells was monitored by Phytohemagglutinin (PHA)-stimulation and T-cell rosette formation. In a human marrow transplant situation it appears that a better yield of CFU-c is necessary than is afforded by albumin gradient technique.
Asunto(s)
Células de la Médula Ósea , Médula Ósea , Separación Celular , Albúminas , Células Madre Hematopoyéticas , Humanos , Lectinas , MétodosRESUMEN
In contrast to other cells stimulated lymphocytes release substances probably cytotoxic which are incorporated by the target cells. The cellular material is released by tearing off parts of fine processes which the lymphocytes extend on to the surface of the target cells. This explains the before mentioned observations that the cell destruction mediated by lymphocytes depends absolutely on a close contact between the lymphocytes and the target cells.