RESUMO
The semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein in microtiter plates, was used for in vitro evaluation of Cladribine (2-chlorodeoxyadenosine, CdA) interactions with five standard antileukemic drugs: amsacrine (Am), etoposide (VP16), daunorubicin (Dnr), cytosine arabinoside (AraC), and mitoxantrone (Mit). Samples from 31 patients with acute myelocytic leukemia (AML) were tested with continuous drug exposure. A large heterogeneity with respect to cell kill was observed for all combinations tested. An additive model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) only for CdA+AraC. When the frequency of additive and synergistic interactions were calculated according to the multiplicative concept for drug interactions, the highest frequencies were observed for CdA+AraC and CdA+Dnr. This interaction pattern was confirmed by isobologram analysis. Cross-resistance analysis revealed high correlations between CdA and AraC whereas the correlations were weaker between CdA and the other drugs. The highest frequency of synergistic interactions was obtained for AraC+CdA, despite their cross-resistance. Of the non-cross-resistant drugs tested, Dnr appears to be the most effective adjunct to CdA in terms of interactions at the cellular level.
Assuntos
Antineoplásicos/farmacologia , Cladribina/farmacologia , Leucemia Mieloide Aguda/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amsacrina/farmacologia , Citarabina/farmacologia , Daunorrubicina/farmacologia , Interações Medicamentosas , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Etoposídeo/farmacologia , Feminino , Fluoresceínas , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/patologiaRESUMO
Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine + vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 patients randomized to prednimustine and vincristine (15 adequately treated), three entered a complete remission and one a partial remission. Four further patients went into complete remission after a switch to other treatment modalities. Of 34 patients randomized to cycles of ARA-C and thioguanine (22 adequately treated), four entered a complete remission and three a partial remission with the correct program. One patient entered a remission with intermittent cytosine arabinoside + thioguanine (wrong program) and one further patient entered a complete remission after a switch to prednimustine and vincristine. Prednimustine + vincristine did not appear to be superior to treatment with cytosine arabinoside thioguanine cycles for elderly patients with ANLL.
Assuntos
Clorambucila/análogos & derivados , Citarabina/uso terapêutico , Leucemia/tratamento farmacológico , Prednimustina/uso terapêutico , Tioguanina/uso terapêutico , Vincristina/uso terapêutico , Doença Aguda , Idoso , Contagem de Células Sanguíneas , Citarabina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednimustina/efeitos adversos , Tioguanina/efeitos adversos , Vincristina/efeitos adversosRESUMO
Sixty consecutive patients, 15-60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1 + ARA-C 2 mg/kg body weight on days 1-5; R2, DNR 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8. Maintenance treatment consisted of monthly courses of DNR 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1-5, alternating with thioguanine 2 mg/kg PO on days 1-5 combined with ARA-C 1 mg/kg IV on days 1-5. Fourteen patients of 20 went into complete remission with R1, 13 or 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer 'minor' cardiac abnormalities than treatment with free DNR in the same dosage schedule.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Adutos de DNA , DNA/uso terapêutico , Daunorrubicina/uso terapêutico , Leucemia/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Envelhecimento , Antibióticos Antineoplásicos/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Ensaios Clínicos como Assunto , DNA/efeitos adversos , Daunorrubicina/efeitos adversos , Feminino , Cardiopatias/induzido quimicamente , Humanos , Imunoterapia , Masculino , Pessoa de Meia-IdadeRESUMO
Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.
Assuntos
DNA/uso terapêutico , Daunorrubicina/uso terapêutico , Leucemia/tratamento farmacológico , Doença Aguda , DNA/efeitos adversos , Daunorrubicina/efeitos adversos , Estudos de Avaliação como Assunto , Humanos , Pessoa de Meia-Idade , Fatores de TempoRESUMO
In the light of previous findings that treatment of leukemia patients with DNA-linked doxorubicin gave higher doxorubicin concentrations in leukemic cells than treatment with doxorubicin alone, the Leukemia Group of Middle Sweden performed a randomized clinical trial to compare the effects of doxorubicin and doxorubicin-DNA in patients with acute non-lymphoblastic leukemia. One hundred and twenty consecutive patients within the age range 15 to 60 years were randomized to one of three treatment groups. In two of these, remission induction treatment was performed with prednisolone, vincristine, ara-C and thioguanine combined with either doxorubicin or doxorubicin-DNA. Patients entering a complete remission received intensive consolidation during 16 months with 4 courses each of doxorubicin (+/ - DNA)/ara-C, doxorubicin (+/ - DNA)/azacytidine, ara-C and amsacrine. The third treatment group followed a protocol from a previous study with daunorubicin and ara-C for induction therapy and a less intensive maintenance therapy. No further patients were assigned to this "control" group after 3 years or to the two other groups after 6 years. This report is based on a follow-up 31 months thereafter. The overall rate of complete remission was 67% and the mean time to complete remission was 71 days, with no differences between the treatment groups. Patients treated with the doxorubicin-DNA conjugate had a significantly longer survival [median for all patients 27.2 months (p < 0.01) and for patients in CR 47.0 months (p < 0.025)] and longer duration of first remission (median 23.6 months, p < 0.025) than the other groups. There were significantly fewer reports of cardiotoxicity (p < 0.05) and severe intestinal toxicity (p < 0.02) in patients treated with the doxorubicin-DNA conjugate and there was a tendency towards less hepatic (p < 0.08) and renal toxicity (p < 0.08). The frequency of myelosuppression, fever and infectious complications was similar in all three groups. Complex binding to DNA appears to increase the therapeutic effects and reduce some toxic effects of doxorubicin in patients with ANLL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adutos de DNA , DNA/uso terapêutico , Doxorrubicina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Amsacrina/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Esquema de Medicação , Humanos , Leucemia Mieloide Aguda/mortalidade , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Análise de Sobrevida , Tioguanina/administração & dosagem , Vincristina/administração & dosagemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Terapia Combinada , Feminino , Humanos , Hidroxiureia/uso terapêutico , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transplante AutólogoAssuntos
Formação de Anticorpos , Asparaginase/uso terapêutico , Leucemia , Doença Aguda , Adulto , Anticorpos/análise , Asparaginase/efeitos adversos , Asparaginase/sangue , Medula Óssea/metabolismo , Células da Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade/etiologia , Imunoglobulina E/análise , Isótopos de Iodo , Leucemia/tratamento farmacológico , Leucemia/enzimologia , Leucemia/imunologia , Leucemia/metabolismo , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Trítio , Valina/metabolismoAssuntos
Abuso Sexual na Infância/diagnóstico , Imperícia , Pré-Escolar , Atenção à Saúde , Erros de Diagnóstico , Humanos , Masculino , SuéciaAssuntos
Leucemia , Linfoma , Complicações Hematológicas na Gravidez , Doença Aguda , Corticosteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Doença Crônica , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológicoAssuntos
Dieta , Fenômenos Fisiológicos da Nutrição , Deficiência de Vitamina B 12 , Vitamina B 12 , Adulto , Anemia Perniciosa , Feminino , Humanos , Absorção Intestinal , Fator Intrínseco , Síndromes de Malabsorção/tratamento farmacológico , Masculino , Necessidades Nutricionais , Gravidez , Vitamina B 12/metabolismo , Vitamina B 12/uso terapêuticoRESUMO
A health examination survey showed that 5.7% of 2322 middle-aged men had a haematocrit value below 40%. Only 1.2% had two consecutive low values. 14 men had no bone marrow haemosiderin and increased their haematocrits following iron therapy. In 13 men with no cause of the anaemia detected there was also a significant increase in haematocrit following therapy. The true prevalence of iron deficiency anaemia in this population may be estimated to about 1%.
Assuntos
Anemia/epidemiologia , Fatores Etários , Anemia/etiologia , Hematócrito , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , SuéciaRESUMO
Determination of the fibrinolytic activity should be performed in patients with recurrent thromboembolic disease. As a screening procedure we suggest the euglobulin clot lysis time test after venous occlusion. This test is sufficiently reliable and easier to perform than the fibrin plate method, especially outside coagulation laboratories.
Assuntos
Testes de Coagulação Sanguínea/métodos , Fibrinólise , Soroglobulinas/fisiologia , Tromboflebite/sangue , Adulto , Idoso , Feminino , Fibrina/análise , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Eleven patients with recurrent venous thrombosis or thrombophlebitis and a decreased fibrinolytic activity after venous occlusion were given a phenformin-like substance, moroxydine chloride, for 6 months. No sustained increase in the fibrinolytic activity was observed after moroxydine treatment.