Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoglobulina D/sangue , Mieloma Múltiplo , Síndromes Mielodisplásicas , Cariótipo Anormal , Idoso de 80 Anos ou mais , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Eritroblastos/metabolismo , Eritroblastos/patologia , Eritropoetina/administração & dosagem , Feminino , Humanos , Imunoglobulina D/genética , Melfalan/administração & dosagem , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/dietoterapia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismoRESUMO
PURPOSE: L-ascorbic acid (LAA) modifies the in vitro growth of leukemic cells from approximately 50% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). To test the hypothesis that depletion of LAA, alternating with supplementation to prevent scurvy, would provide therapeutic benefit, a single-arm pilot trial was conducted (ClinicalTrials.gov identifier: NCT00329498). Experimental results: During depletion phase, patients with refractory AML or MDS were placed on a diet deficient in LAA; during supplementation phase, patients received daily intravenous administration of LAA. An in vitro assay was performed pretherapy for LAA sensitivity of leukemic cells from individual patients. RESULTS: Of 18 patients enrolled, eight of 16 evaluable patients demonstrated a clinical response. Responses were obtained during depletion (four patients) as well as during supplementation (five patients) but at a pharmacologic plasma level achievable only with intravenous administration. Of nine patients for whom the in vitro assay indicated their leukemic cells were sensitive to LAA, seven exhibited a clinical response; compared with none of six patients who were insensitive to LAA. CONCLUSIONS: The clinical benefit, along with a conspicuous absence of significant adverse events, suggests that further testing of LAA depletion alternating with pharmacologic dose intravenous supplementation in patients with these and other malignancies is warranted.
Assuntos
Ácido Ascórbico/metabolismo , Ácido Ascórbico/uso terapêutico , Leucemia Mieloide Aguda/dietoterapia , Síndromes Mielodisplásicas/dietoterapia , Adulto , Idoso , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Estudos Prospectivos , Medição de RiscoRESUMO
The treatment of myelodysplastic disorders with vitamins A and D or derivatives and nutrients has been less than satisfactory. Combinations of vitamin D3 and 13-CRA with or without cytosine arabinoside appear to offer no advantage over any of the single agents alone. Until other vitamin D derivatives are developed that are effective but do not cause hypercalcemia, vitamin D3 cannot be recommended for the treatment of MDS. 13-CRA has been shown to be effective in some patients with MDS; however, it cannot be recommended as standard therapy because of the conflicting data cited above. Further clinical trials with 13-CRA perhaps in combination with vitamin E or colony-stimulating factors are clearly indicated for this disease for which we have no effective therapy.
