RESUMEN
Treatment with recombinant human erythropoietin (rhEPO) improves anaemia in approximately 20% of the patients with myelodysplastic syndromes (MDS). Recent reports suggest that a combination treatment with rhEPO plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) given for up to 18 weeks may result in a higher erythroid response rate than with rhEPO alone. We investigated the potential advantage of an even more prolonged schedule of combined rhG-CSF and rhEPO treatment to obtain and maintain stable responses. In a phase II study, 33 patients with MDS [17 with refractory anaemia (RA), eight with RA with ringed sideroblasts (RARS), eight with RA with excess blasts (RAEB) with bone marrow blast counts less than 20%] were scheduled to receive at least 36 weeks of combined therapy with rhG-CSF and rhEPO. Seventeen of 28 evaluable patients demonstrated an erythroid response [61%; 95% confidence interval (CI) 41-78] after 12 weeks of treatment. The erythroid response rate was 80% (20 of 25 evaluable patients; 95% CI 59-93) after 36 weeks. Seven of these responses developed between week 12 and week 36, whereas two initially responding patients became refractory. The cytokine therapy was generally well tolerated. Nineteen of the 20 patients responding after 36 weeks continued to be treated with both cytokines. After 1 year and 2 years of continuous combined treatment, 50% of the initially included patients showed a continuing response. Our results suggest that a prolonged combination treatment with rhG-CSF and rhEPO is highly effective in achieving a stable and long-lasting erythroid response in many patients with MDS and low blast count.
Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Síndromes Mielodisplásicos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anemia/sangre , Supervivencia sin Enfermedad , Esquema de Medicación , Quimioterapia Combinada , Recuento de Eritrocitos , Eritropoyetina/uso terapéutico , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Proteínas Recombinantes , Factores de Tiempo , Resultado del TratamientoRESUMEN
We performed a phase II study to determine the efficacy of maximal cytoreductive therapy with up to five cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for patients with advanced relapsed or refractory indolent lymphoma. Thirty-two patients with primary refractory or relapsed indolent lymphoma were treated with the Dexa-BEAM regimen. Thirteen patients had primary refractory disease, 4 patients partial remission, and 15 patients first or subsequent relapse. Patients achieving PR or CR received HDCT with ASCT. The conditioning regimen used was BEAM (carmustine [BCNU], etoposide, cytarabine, and melphalan). Twenty-two patients responded to Dexa-BEAM resulting in a response rate of 78%. Maximum response was observed after 3.2 (range 2-5) courses. One patient with progressive disease died in septic shock during neutropenia. Nineteen patients with partial or complete remission after Dexa-BEAM received HDCT. Hematopoietic stem cells (HSC) were collected after two cycles of Dexa-BEAM. The median number of CD34+ HSC reinfused was 3.1 x 10(6)/kg (range 1.6-8.2 x 10(6)/kg). There was no transplantation-related death. All patients receiving HDCT achieved complete remission. Overall survival (OS) and freedom from treatment failure (FFTF) for all patients are estimated to be 68% and 65% at two years, respectively. With a mean follow-up of 20 months (range 8-42 months), 16/19 patients receiving HDCT are in continuous complete remission. The Dexa-BEAM regimen is effective in overcoming drug resistance in patients with indolent lymphoma who failed to respond to conventional treatment or who relapsed. The CR rate of 100% of those patients receiving HDCT and ASCT after maximal cytoreductive treatment with Dexa-BEAM suggests the use of HDCT at the time of maximal response.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma/tratamiento farmacológico , Terapia Recuperativa , Adulto , Carmustina/administración & dosificación , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Inducción de Remisión , Análisis de Supervivencia , Acondicionamiento Pretrasplante , Trasplante AutólogoRESUMEN
Mantle-cell lymphoma (MCL) is not a curable disease using conventional chemotherapy. Patients with MCL have the shortest median time to progression and the shortest median survival of all lymphoma subtypes after first-line treatment. In the present study we determined the efficacy of maximal cytoreductive therapy with up to four cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell support (ASCT) for patients with advanced relapsed or refractory MCL. Nine consecutive patients with relapsed or refractory MCL were included. Three patients had partial remission (PR), three patients progressive disease (PD) upon first line tretment, and three patients first or subsequent relapse. After 2 to four cycles of Dexa-BEAM eight patients achieved complete remission (CR), resulting in a response rate of 88%. Six of 8 patients responding to Dexa-BEAM received high-dose chemotherapy HDCT (BEAM) and autologous hematopoietic stem cell transplantation (ASCT). With a median follow up of 24 months six patients are alive. Five of those six patients are still in contiuous CR (range 13-54 months).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto/terapia , Terapia Recuperativa , Adulto , Carmustina/administración & dosificación , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Inducción de Remisión , Análisis de Supervivencia , Trasplante AutólogoRESUMEN
For autologous stem cell transplantation, it is common practice to infuse at least 2 x 10(6)/kg CD34+ cells to ensure rapid engraftment. However it was recently claimed that increasing the threshold to 5 x 10(6)/kg leads to a faster platelet engraftment. To evaluate these threshold values in our patient population we undertook a retrospective analysis of 127 autologous transplants performed at our institution between 1992 and 1998. Diagnoses included Hodgkin's and non-Hodgkin's lymphoma, myeloma, acute leukaemias and solid tumours. The transplant was peripheral blood stem cells in 107 cases and CD34-selected peripheral blood stem cells in 20 cases. The median number of transplanted CD34+ cells was 3.2 x 10(6)/kg (range 0.64-25.9 x 10(6)/kg). Haematopoietic recovery to a neutrophil count >0.5 x 10(9)/l took a median of 10 (range 5-16) days from transplant. When comparing patients receiving at least 5 x 10(6)/kg and 2-5 x 10(6)/kg CD34+ cells we found a significant reduction in the median number of days with fever (1 vs 3.5 days, P = 0.0025), incidence of fever (78.8 vs 92.1%, P = 0.032) as well as duration of antibiotic treatment (7 vs 10 days, P = 0.038). This was paralleled by a faster neutrophil recovery to 0.5 x 10(9)/l (9 vs 10 days, P = 0.047). There was no significant difference in the number of platelet or red cell transfusions between the two groups. We conclude that transplantation with a stem cell dose of at least 5 x 10(6)/kg CD34+ cells reduces infectious complications and should thereby increase the safety of this type of therapy while reducing duration (and cost) of antibiotic therapy. The transplantation threshold should thus not remain at 2 x 10(6)/kg particularly in patients with a good stem cell mobilisation capacity.
Asunto(s)
Antibacterianos/uso terapéutico , Antígenos CD34/análisis , Fiebre/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
BACKGROUND: Disease status before high-dose chemotherapy with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is an important predictor of transplantation-related toxicity and event-free survival (EFS) for patients with relapsed or refractory Hodgkin's disease (HD). We performed a phase II study in patients with relapsed or refractory HD to evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose chemotherapy with ABMT or PBSCT. PATIENTS AND METHODS: Twenty-six patients (median age 30, range 20-40 years) were treated with 2-4 courses of dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as salvage chemotherapy in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received high-dose chemotherapy with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide, carmustine, etoposide). RESULTS: Eighteen patients responded to Dexa-BEAM, resulting in a response rate of 69%. At the time of transplant 16 patients were in CR two patients in PR. At present 14 patients transplanted are in continuous CR (median follow-up 40 months, range 14-60 months). Two patients with PR after four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two patients with CR at the time of transplant relapsed after nine and 13 months respectively. Eight patients had rapid progressive disease after 2-4 cycles of Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis after four cycles of Dexa-BEAM. There was no transplantation-related death. CONCLUSION: These data suggests the use of high-dose chemotherapy followed by stem cell transplantation at the time of maximal response.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Recurrencia Local de Neoplasia/terapia , Terapia Recuperativa , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carmustina/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Etopósido/administración & dosificación , Femenino , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Elderly patients (age > or = 60 years) with acute myeloid leukemia (AML) have unfavourable prognoses when polychemotherapy regimens are used, because therapy response is characterized by low remission rates, short remission duration and high toxicity. PATIENTS AND METHODS: A phase II trial in elderly AML patients was conducted to determine the efficacy of two induction courses of a moderately-dosed combination of aclarubicin (25 mg/m2, 30 min i.v., days 1-4), etoposide (100 mg/m2, 30 min i.v., days 1-3) and conventional-dose cytosine arabinoside (ara-C, 100 mg/m2, c.i.v., days 1-3 and 30 min i.v., q 12 hours, days 4-7) (AVA-7), followed by one consolidation treatment using a reduced-dose schedule over five days (AVA-5) after three months in CR. RESULTS: Thirty-two AML patients with a median age of 66.2 years (range 60-76) were included in the study: three of them had histories of preexisting myelodysplasia and one of polycythemia vera. Following 1-2 courses of AVA-7 17 patients (53%) achieved CR, two PR (6%), and nine had resistant disease (28%); the overall response rate was thus 59%. Toxicity was significant but acceptable, with an overall treatment-related death rate of five of 32 patients (16%) after 63 courses of AVA. The median disease-free survival (DFS) was 12 months, and the median survival of all patients was 16.6 months. CONCLUSIONS: These results indicate that the combination of aclarubicin, etoposide and conventional-dose ara-C is effective in elderly AML patients. The relatively brief remission duration requires new consolidation and maintenance therapy approaches.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Aclarubicina/administración & dosificación , Anciano , Análisis de Varianza , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , MasculinoAsunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Estadificación de Neoplasias , Tasa de Supervivencia , Insuficiencia del TratamientoAsunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Expresión Génica , Leucemia Mieloide Aguda/genética , Reacción en Cadena de la Polimerasa , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , ADN Polimerasa Dirigida por ARNRESUMEN
Blastoschizomyces capitatus (Trichosporon capitatum) is an uncommon fungal pathogen. Infections have mostly been seen in immunocompromised patients and use of broad spectrum antibiotics was identified as a risk factor. Treatment has been extremely difficult. A report is presented about a case of fatal B. capitatum infection with clinical septicemia and multiorgan failure during intravenous liposomal amphotericin B therapy.
Asunto(s)
Anfotericina B/administración & dosificación , Micosis/tratamiento farmacológico , Trichosporon/aislamiento & purificación , Adulto , Portadores de Fármacos , Resultado Fatal , Humanos , Leucemia Linfoide/complicaciones , Liposomas , Masculino , Neutropenia/complicaciones , Insuficiencia del TratamientoRESUMEN
Five patients with non-cytotoxic drug-induced agranulocytosis were treated with recombinant human granulocyte-colony-stimulating factor (rh-G-CSF). The drugs involved were dipyrone, captopril, clozapine and carbimazole. Bone marrow examination revealed a depleted granulopoiesis with normal erythro- and megakaryocytopoiesis. After discontinuation of the suspected drug, rh-G-CSF was administered daily at 5 microg/kg subcutaneously. The neutrophil counts were recovered between day 6 and 12 and patients were discharged from hospital shortly afterwards. Compared to data from the literature, the neutrophil recovery appeared to be faster than expected without the use of haematopoietic growth factors. In conclusion, rh-G-CSF at a standard dose of 5 microg/kg seems to be an effective treatment for drug-induced agranulocytosis.
Asunto(s)
Agranulocitosis/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Administración Cutánea , Adulto , Anciano , Agranulocitosis/etiología , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Masculino , Proteínas RecombinantesRESUMEN
Bispecific antibodies (bi-MABs) can be used to target T cells to autologous tumor cells. It has been shown that the activation of resting human T cells requires two independent signals, namely the cross-linking of the T-cell receptor (TCR)-CD3 complex together with the CD28 homodimer. In the present study, we demonstrate the activation of T cells from patients with chronic lymphocytic leukemia (CLL) using bi-MABs against the CD3 and CD19 antigens (CD3 x CD19) in combination with monospecific, bivalent antibodies against the CD28 antigen. Mononuclear cells from patients with CLL were cultured with the bi-MAB CD3 x CD19 and monospecific CD28 antibodies. The CD3 x CD19 bi-MABs were isolated by the hybridoma-hybridoma fusion technique and purified by hydrophobic interaction chromatography. T-Cell activation as demonstrated by increased proliferation, upregulation of T-cell activation markers (CD25, CD38), and cytotoxicity against autologous CLL cells and allogeneic B cells was shown in seven of eight CLL specimens. The stimulation with CD3 x CD19 bi-MABs with CD28 antibodies preferentially induced proliferation of CD4+ T cells. The effective dose of purified antibodies required for optimal T-cell activation was 100 ng/mL in vitro, which suggests that this antibody combination may be useful for immunotherapy of patients with B-CLL.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos B/inmunología , Linfocitos B/inmunología , Antígenos CD28/inmunología , Complejo CD3/inmunología , Citotoxicidad Inmunológica , Leucemia Linfocítica Crónica de Células B/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Especificidad de Anticuerpos , Antígenos CD19 , Línea Celular , Femenino , Humanos , Inmunoterapia/métodos , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Interleucina-6/biosíntesis , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Linfocítica Crónica de Células B/terapia , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Receptores de Superficie Celular/inmunologíaRESUMEN
Diagnostic results from cytomorphology and immunocytology of aspirated bone marrow (BM) were compared with the findings from standard trephine histology of 100 adult patients with non-leukaemic non-Hodgkin's lymphomas (NHL) in a retrospective study. Immunocytological investigations were performed by the immunoenzymatic APAAP-technique on BM smears monoclonal antibodies against CD19, Cd3, CD10 or TdT antigens and determination of positive cells in relation to total BM leucocytes. Corresponding results were obtained for trephine histology and for the combination of cytomorphology and immunocytology in 93/100 cases. Four cases with BM involvement by trephine histology were missed by the combination of immunocytology and cytomorphology. In turn, three cases negative by trephine histology, were found to be positive by the combination of immunocytology and cytomorphology. Immunocytochemistry considerably increased the number of true positive detected BM-infiltrations by cytomorphology in low grade B-cell lymphoma from 58% to 97%. For the diagnosis of BM involvement in high-grade NHL cytomorphology of the aspirate was of equal sensitivity to the biopsy and was always confirmed by immunocytology. The high diagnostic sensitivity of immunocytology was mainly due to high B-cell counts in BM involved by B-cell lymphoma (means = 38%, s = 23) in contrast to low B-cell counts in BM not involved by NHL (means = 4.5%, s = 3.8). We conclude from our data that immunocytology in addition to standard cytomorphology improves diagnostic sensitivity in the detection of BM involvement by NHL.
Asunto(s)
Médula Ósea/patología , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/patología , Adolescente , Adulto , Anticuerpos Monoclonales , Antígenos CD/análisis , Antígenos CD/inmunología , Antígenos CD19 , Antígenos de Diferenciación de Linfocitos B/análisis , Antígenos de Diferenciación de Linfocitos B/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Linfocitos B/fisiología , Biopsia , Médula Ósea/fisiología , Complejo CD3/análisis , Complejo CD3/inmunología , ADN Nucleotidilexotransferasa/inmunología , Histocitoquímica , Humanos , Inmunohistoquímica , Linfoma de Células B/diagnóstico , Linfoma de Células B/epidemiología , Linfoma de Células B/patología , Linfoma no Hodgkin/epidemiología , Neprilisina/análisis , Neprilisina/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Estudios Retrospectivos , Linfocitos T/inmunología , Linfocitos T/patología , Linfocitos T/fisiologíaRESUMEN
Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.
Asunto(s)
Trasplante de Médula Ósea , Hidroxiurea/uso terapéutico , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Busulfano/uso terapéutico , Femenino , Alemania , Humanos , Interferón-alfa/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , PronósticoAsunto(s)
Células Madre Hematopoyéticas/patología , Leucemia Mielomonocítica Crónica/patología , Anciano , Transfusión Sanguínea , Células de la Médula Ósea , Transfusión de Eritrocitos , Trastornos Hemorrágicos/etiología , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/terapia , Masculino , Transfusión de PlaquetasRESUMEN
Aggressive oncological chemotherapy often impairs the nutritional status of tumor patients. To evaluate the pathogenetic mechanisms, food intake in 13 cancer patients was investigated in correlation with nitrogen losses, N balances, muscle wasting, and weight course, during cytostatic therapy. Median daily N and energy intakes were reduced only in patients with weight loss [0.55 g protein, 16.5 kcal/kg ideal body wt (IBW)]. Patients with constant weight had the same intake as control subjects (1.27 g protein, 37.2 kcal IBW). N balances and creatinine height index (CHI) correlated with daily nutrient intake. Fecal N excretions did not correlate with urinary losses; there was no excess of fecal N loss because of cytostatic treatment. The impairment of cancer patients' nutritional status seems to depend primarily on the decrease of spontaneous oral intake as a consequence of the side effects of tumor therapy. Changes in CHI, compared before and after chemotherapy, indicated muscle wasting of weight-losing patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Ingestión de Energía , Neoplasias/metabolismo , Nitrógeno/metabolismo , Adulto , Peso Corporal/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Fenómenos Fisiológicos de la NutriciónRESUMEN
A human malignant melanoma was grown in nude mice. The tumour showed an exponential growth for several weeks which gradually slowed down, until following week 8 the tumour growth ceased. The reasons for this growth pattern were examined by labelling techniques (PLM, LI). The tumour cell production as quantified by the growth fraction, showed only a moderate reduction which, taken alone, could not explain the growth cessation. The important mechanism seems to be an increased loss of tumour cells during the intermitotic interval. While the loss of cells/h remains constant the total intermitotic cell loss is increased because the cell cycle times are prolonged by 50% from the exponential phase (45 h in week 3) to the plateau phase (66 h in week 8).
Asunto(s)
Melanoma/patología , Adulto , Animales , División Celular , Femenino , Humanos , Cinética , Masculino , Ratones , Ratones Endogámicos , Ratones Desnudos , Mitosis , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
This report describes some experimental and clinical studies showing the following: (1) in animals under protection of mesna the dose of ifosfamide (Ifo) can be increased significantly; (2) fractionated administration of Ifo, cyclophosphamide (CPA), or the stabilized metabolite of cyclophosphamide (ASTA Z 7557) is less toxic than single push-injection of the same total daily dose and therapeutically more effective; and (3) in humans under the protection of mesna the continuous infusions of ifosfamide over 5 days leads to an increase of the MTD compared with single daily short-term infusion and responses in some solid tumors, e.g., soft tissue sarcomas.
Asunto(s)
Ciclofosfamida/análogos & derivados , Ciclofosfamida/administración & dosificación , Ifosfamida/administración & dosificación , Neoplasias/tratamiento farmacológico , Animales , Ensayos Clínicos como Asunto , Ciclofosfamida/toxicidad , Humanos , Ifosfamida/toxicidad , Infusiones Parenterales , Riñón/efectos de los fármacos , Dosificación Letal Mediana , Masculino , Mesna/administración & dosificación , Ratones , Ratones Endogámicos , Persona de Mediana EdadRESUMEN
ASTA Z 7557 is a stabilized cytostatic metabolite of cyclophosphamide which forms crystals at room temperature and releases 4-OH-cyclophosphamide in aqueous solution. The LD50/30 in mice after push injection is 417 mg/kg, after fractionated administration (q 6 hours X 4) 794 mg/kg. Daily treatment times 5 gives a LD50/30 value of 200 mg/kg. Depression of nucleated bone marrow cells and of leukocytes in the peripheral blood is observed after treatment. Recovery is slow. This holds true for push and fractionated administration. ASTA Z 7557 is a powerful cytostatic drug for treatment of an Ehrlich ascites tumor, a Lewis lung and a mammary carcinoma. Of two human tumor xenografts a malignant amelanotic melanoma responded with slight growth delay, whereas a gastric cancer did not.