RESUMEN
PURPOSE: The present study aimed to investigate the efficacy and severity of adverse effects of HCAG and CAG re-induction chemotherapy in elderly low- and intermediate-risk group patients diagnosed with acute myeloid leukemia (AML) following induction failure. METHODS: A total of 94 AML patients were enrolled in the study, of whom 46 were treated with HCAG chemotherapy, while 48 were treated with CAG chemotherapy. RESULT: The complete remission (CR) was 39.6% in the patients with HCAG, while the CR was 33.3% in the CAG group. The overall remission (ORR) was 63.0% and 43.5% in patients of the HCAG and CAG groups, respectively (P = 0.038). The median survival time of progression free survival (PFS) was 8.0 (95% CI 3.843-10.157) months in the HCAG group and 7.0 (95% CI 2.682-13.318) months in the CAG group (P = 0.032). A total of 31 patients in the HCAG group suffered from grade 4 hematological toxicity, whereas 29 patients were treated with CAG (P = 0.622). A total of 27 (58.7%) cases indicated apparent pulmonary infection in the HCAG group, while 25 (52.1%) were noted with this complication in the CAG group (P = 0.519). Oral cavity toxicity was evident for 13 (28.3%) and 11 (23.0%) cases in the HCAG and CAG groups, respectively (P = 0.216). CONCLUSION: The HCAG regimen was more effective than the CAG regimen in elderly low- and intermediate-risk group patients diagnosed with acute myeloid leukemia although the HCAG regimen exhibited similar toxicity with that of the CAG group.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Homoharringtonina/uso terapéutico , Quimioterapia de Inducción/métodos , Leucemia Mieloide Aguda/tratamiento farmacológico , Aclarubicina/efectos adversos , Aclarubicina/uso terapéutico , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/efectos adversos , Citarabina/uso terapéutico , Esquema de Medicación , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Homoharringtonina/efectos adversos , Humanos , Quimioterapia de Inducción/efectos adversos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Inducción de Remisión , Retratamiento/métodos , Estudios Retrospectivos , Factores de Riesgo , Terapia Recuperativa , Método Simple Ciego , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
PURPOSE: The aim of the present study was to investigate the efficacy and adverse effects of HCAG and FLAG re-induction chemotherapy in acute myeloid leukemia (AML) patients of low- and intermediate-risk groups following induction failure. METHODS: A total of 98 AML patients were enrolled. Among these subjects, 47 patients were treated with HCAG chemotherapy, while 51 patients were treated with FLAG chemotherapy. RESULT: The complete remission (CR) and overall remission (OFF) were 24% and 38%, respectively in patients with HCAG induction chemotherapy, while the corresponding percentages were 28% and 42% in subject receiving FLAG chemotherapy. The median survival time of progress-free survival (PFS) was 29.8 (95% CI 23.749-35.851) months in the HCAG group and 30.8 (95% CI 21.728-39.872) months in the FLAG group (P = 0.620). A total of 42 patients in the HCAG group suffered from grade 4 hematological toxicity, while this adverse reaction was noted for all patients who were treated with FLAG chemotherapy (P = 0.023). A total of 19 cases indicated apparent nonhematological toxicity in the HCAG group, while only 40 (78.4%) were noted with these adverse reactions in the FLAG group (P = 0.000). CONCLUSION: The HCAG regimen exhibited a similar effect compared with the FLAG regimen in low- and intermediate-risk groups, although the HCAG regimen significantly decreased the toxicity compared with that noted in the FLAG regimen group.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción/métodos , Leucemia Mieloide Aguda/tratamiento farmacológico , Aclarubicina/administración & dosificación , Aclarubicina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Esquema de Medicación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Homoharringtonina/administración & dosificación , Homoharringtonina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Riesgo , Método Simple Ciego , Insuficiencia del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
The K562 cell line has erythroid origin and is used for the study of fetal haemoglobin (HbF) production after treatment with several drugs, such as hydroxyurea, cisplatin and cytosine arabinoside (Ara C). It represents an important tool for the study of cancer differentiation therapy and treatment of thalassaemia and sickle cell disease. Although subject to intense research, the mechanisms involved in the induction of HbF are not fully established, and the regulation of several genes and signalling pathways has been proposed. Using the methodology of differential display, we investigated the changes in gene expression in K562 cells treated with doxorubicin and aclarubicin, which induce HbF expression and cell cycle arrest. Several genes were shown to present differential expression patterns, many of them related to the iron signalling pathway. Particular attention was given to Ndrg1, expressed as early as 24 h after treatment, which can be regulated by iron and is involved with blocking of the cell cycle. A review of the literature shows that, similar to doxorubicin and aclarubicin, most of the drugs used to induce HbF present some kind of effect on the iron signalling pathway, activating in the cells the machinery necessary for the incorporation of extracellular iron. Considering these results, as well as the fact that in erythroid cells the synthesis of haemoglobin is of vital importance, we propose that the production of fetal haemoglobin in erythroid cells is highly dependent on the iron signalling pathway.
Asunto(s)
Aclarubicina/administración & dosificación , Doxorrubicina/administración & dosificación , Hemoglobina Fetal/biosíntesis , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Transducción de Señal/efectos de los fármacos , Antibióticos Antineoplásicos/administración & dosificación , Diferenciación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células K562RESUMEN
Anthracyclines have been widely used as anticancer drugs against different types of human cancers. The present study evaluated the mutagenic and recombinagenic properties of two anthracycline topoisomerase II (topo II) poisons, daunorubicin (DNR) and idarubicin (IDA), as well as the related topo II catalytic inhibitor aclarubicin (ACLA), using the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. The three anthracyclines were positive in this bioassay, producing mainly mitotic homologous recombination. The results for spot-size distribution and recombinagenic activity indicate that recombinational DNA damage accounts for approximately 91, 86, and 62% of DNR, IDA, and ACLA genotoxicity, respectively. Besides being a catalytic inhibitor of topo II, ACLA is also a topoisomerase I (topo I) poison. This dual topo I and II inhibitory effect, associated with its DNA-intercalating activity, could contribute to the activity of ACLA in the SMART assay.
Asunto(s)
Aclarubicina/toxicidad , Daunorrubicina/toxicidad , Idarrubicina/toxicidad , Mutagénesis/efectos de los fármacos , Inhibidores de Topoisomerasa , Aclarubicina/química , Animales , Bioensayo , Análisis Mutacional de ADN , Daunorrubicina/química , Relación Dosis-Respuesta a Droga , Drosophila , Idarrubicina/química , Alas de Animales/anatomía & histologíaRESUMEN
Aclacinomycin (ACM) is an oncostatic of the anthracycline family, largely used in patients and experimentally in mice. ACM has been reported to enhance phagocytosis, secretion of free oxygen radicals and of interleukin 1. Its injection is also followed by an increase of the cytotoxic and cytostatic activity of murine peritoneal macrophages. In the present work we investigated whether ACM modifies the antigen-presenting cell capacity of murine peritoneal macrophages. Purified T lymphocytes were cultured with peritoneal macrophages from either normal or ACM treated mice (4 mg/kg day -4) which were previously incubated with phytohemagglutinin. The T cell proliferative response was greater in cultures with normal macrophages, indicating that macrophages from ACM-treated mice had a better antigen presenting activity than normal untreated macrophages.
Asunto(s)
Aclarubicina/farmacología , Antibióticos Antineoplásicos/farmacología , Células Presentadoras de Antígenos/inmunología , Macrófagos Peritoneales/inmunología , Animales , Inmunidad Celular/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Aclacinomycin (ACM) is an oncostatic substance on the family of the Anthracyclines, with a proven activity in human and rodents. Splenic cells from C57BL/6 ACM injected mice by intraperitoneal or intravenous route four days before their sacrifice showed a significant increase in the proliferative and cytotoxic response respectively measured by incorporation of 3H-TdR and by the liberation of 51Cr when stimulated in vitro with irradiated mouse DBA/2 splenic cells. This response is doses dependent, and one can clearly observe different effects on the proliferative and cytotoxic responses at high doses. The cultures supernatants of splenic cells from mice treated with ACM during allogeneic stimulation showed a greater activity to induce the proliferation of a line of T cytotoxic cells dependent on Interleukin-2. Finally, the cytotoxic activity of splenic cells induced by the allogeneic stimulation in vitro, of mice treated with ACM, was found in a subpopulation of cells non adherent to plastic, mainly made up of lymphocytes.