Assuntos
Neoplasias do Íleo , Valva Ileocecal , Tumores Neuroendócrinos , Humanos , Neoplasias do Íleo/diagnóstico por imagem , Neoplasias do Íleo/cirurgia , Valva Ileocecal/diagnóstico por imagem , Valva Ileocecal/patologia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgiaRESUMO
Treatment of patients with primary mediastinal B-cell lymphoma (PMBCL) remains controversial. We started a controlled clinical trial to evaluate the efficacy and toxicity of a conventional versus more intensive regimen of combined chemotherapy followed by radiotherapy to the mediastinum with the mantle technique. From 1989 to 1997, 68 patients diagnosed with previously untreated PMBCL, aged 18-65 years and negative for immunodeficiency virus test, were considered candidates to receive either conventional chemotherapy with CEOP-Bleo (cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2), prednisone 40 mg/m(2), epirubicin 70 mg/m(2), and bleomycin 10 mg/m(2)) or mega CEOP-Bleo (cyclophosphamide 1000 mg/m(2), epirubicin 120 mg/m(2), vincristine, prednisone, and bleomycin at the same doses) every 21 days for six cycles, followed by radiotherapy to the mediastinum with the mantle technique (35-45 Gy, mean 38 Gy). Complete response (CR) rates were not statistically different: 64% [95 percent confidence interval (CI): 58 percent to 70 percent] for conventional arm vs 81 percent (95 CI: 77-86 percent) in the intensive group (p=0.2). However, failure-free survival (FFS) and overall survival (OS) had statistical differences. At 5 years, actuarial FFS for patients treated with conventional chemotherapy was 51 percent (95 percent CI: 44-59 percent) compared to 70 percent (95 percent CI: 65-76 percent) in the intensive arm (p>0.01). OS rates were also different: 54 percent (95 percent CI: 48-57 percent) vs 70 percent (95 percent CI: 65-76 percent), respectively (p<0.01). Toxicity was mild and no therapy-related deaths were observed. At a median follow-up of 7.3 years, no second neoplasia or acute leukemia has been observed. The international prognostic index was not useful to define clinical risk in this selected group of patients. Multivariate analysis identified pleural and pericardial effusion and chemotherapy regimen as prognostic factors influencing FFS and OS. We feel that patients with PMBCL should be treated with more intensive, but not myeloablative chemotherapy, followed by adjuvant radiotherapy to achieve an improvement in outcome in this setting of patients. Patients with pleural or pericardial effusion are considered at high risk for failure with the actual programs of treatment and probably will be considered for experimental therapeutic approaches.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Prednisona/uso terapêutico , Vincristina/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Linfoma de Células B/radioterapia , Masculino , Neoplasias do Mediastino/radioterapia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Radioterapia Adjuvante , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Presence of late lethal events has been recognized as a complication in patients with malignant lymphoma. We reviewed 714 cases of patients treated during 1975-1995 with a long term follow-up (>4 years) in an attempt to identify all late events secondary to malignant lymphoma, either to the treatment or those which are unrelated. Forty-three patients died, and of these 21 (2.8%) were secondary to relapse and tumor progression; deaths associated with second neoplasm and cardiac events were increased 9.6 fold and 26.4 fold respectively compared to the general population. The risk factors for these complications did not differ from those in previous reports and included alkylating agents and/or radiotherapy for second neoplasms and anthracycline therapy and radiotherapy for cardiac toxicity. Moreover, 10 patients died secondary to non-related events. Nevertheless, at 10 years overall survival was 94% (95% confidence interval (CI): 82% to 98%) and event free survival was 97.1% (95% CI: 81% to 98%), for these patients. Thus, second events, fatal in most cases, will be considered as an expected risk in the treatment of patients with malignant lymphoma. The proposed modifications of therapy many indeed be useful to avoid or diminish these complications in the future.
Assuntos
Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/mortalidade , Adulto , Idoso , Alquilantes/uso terapêutico , Alquilantes/toxicidade , Antraciclinas/uso terapêutico , Antraciclinas/toxicidade , Doenças Cardiovasculares/etiologia , Causas de Morte , Coleta de Dados , Feminino , Humanos , Linfoma de Células B/complicações , Linfoma de Células B/epidemiologia , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Radioterapia Adjuvante/efeitos adversos , RecidivaRESUMO
We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease.
Assuntos
Antineoplásicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Método Duplo-Cego , Feminino , Doença de Hodgkin/mortalidade , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Análise de SobrevidaRESUMO
Based on preclinical and clinical studies which suggested that amifostine can protect against haematological toxicity of cyclophosphamide, we conducted a clinical trial of amifostine and intermediate doses of cyclophosphamide in patients with high-risk malignant lymphoma. 40 patients were enrolled to receive amifostine (910 mg/m2) before cyclophosphamide (1500 mg/m2) for two cycles (10 patients); 20 patients were allocated to receive amifostine/cyclophosphamide only on one cycle (patients were their own control) and 10 patients received cyclophosphamide alone without amifostine protection. Patients who received amifostine had fewer days of severe granulocytopenia (grade III or IV) and infectious episodes, and delay on treatment was minimal. Amifostine was well tolerated; only 2 patients developed transient and mild hypotension. The complete response rate was 72% (29/40). We conclude that amifostine is a good protector against haematological toxicity of cyclophosphamide and did not interfere with tumour response. Clinical trials with increasing doses of cytotoxic drugs or combination chemotherapy are needed to define the role of this myeloprotector agent in the treatment of patients with malignant lymphoma.
Assuntos
Agranulocitose/prevenção & controle , Amifostina/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Medula Óssea/efeitos dos fármacos , Ciclofosfamida/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Agranulocitose/induzido quimicamente , Antineoplásicos Alquilantes/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/prevenção & controleRESUMO
One hundred and sixty nine untreated elderly patients (median age 69 years old; range 60-89 years old) with high or high-intermediate clinical risk non-Hodgkin's lymphoma were enrolled in a controlled clinical trial to evaluate escalated doses of epirubicin in a CEOP-Bleo regimen (cyclophosphamide, vincristine, epirubicin, prednisone and bleomycin), compared to escalated doses of idaurubicin in an CIOP-Bleo regimen (idaurubicin instead of epirubicin). Overall, 71% of the patients in the CEOP-Bleo arm achieved a complete response compared to only 48% in the CIOP-Bleo regimen (p < 0.01). At actuarial 3 year, 72% of the patients treated with the CEOP-Bleo regimen remained alive and free of disease, compared to 34% in the CIOP-Bleo arm (p < 0.01). Dose intensity was 0.86 in the epirubicin regimen, similar to 0.82 in the idaurubicin arm. Toxicities were more frequent and severe in the CEOP-Bleo regimen; however, no death-related treatment was observed in either groups. Cardiac toxicity was also similar in both arms. We conclude that treatment of elderly paitents with aggressive non-Hodgkin's lymphoma should be considered a curative attempt and not only palliative. The use of full doses of chemotherapy should be contemplated in elderly patients. Epirubicin, in escalating doses, is a drug with mild toxicity and improvement in outcome in this setting is observed. We cannot confirm the usefulness of idaurubicin, including escalating doses, in the treatment of patients with aggressive malignant lymphoma, because the complete response rate and survival were worse than other chemotherapy regimens. We feel that the CEOP-Bleo regimen with escalated doses of epirubicin is a useful option in the treatment of elderly patients with aggressive non-Hodgkin's lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Idarubicina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
From January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse-free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen. Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone-containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Análise Atuarial , Adolescente , Adulto , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Mitoxantrona/administração & dosagem , Estadiamento de Neoplasias , Indução de Remissão , Taxa de Sobrevida , Vimblastina , Vincristina/administração & dosagemRESUMO
Seventy patients with previously untreated advanced Hodgkin's disease and without bulky disease were entered in a prospective randomized clinical trial comparing epirubicin in combination with vinblastine, bleomycin, and dacarbazine (EVBD) with a regimen containing mitoxantrone, vinblastine, bleomycin, and dacarbazine (MVBD). Both groups were comparable for the variables of age, sex, stage, and presence of B symptoms and histology. Thirty-one (88%) of EVBD-treated patients achieved a pathologically documented complete remission (CR) compared to the 24 cases (68%) of the MVBD-treated group. After a median follow-up of 36 months, duration of CR is better in the EVBD-treated patients with an actuarial 5-year duration of CR of 80%, statistically different to the MVBD group: 53% (P < 0.01). Both regimens showed the same gastrointestinal toxicity, but the patients treated with the MVBD regimen shown most and severe hematological and cardiac toxicities. Also, biochemical alterations in hepatic test were observed in these patients. The alternative use of epirubicin in combination chemotherapy appears to be as effective in advanced Hodgkin's disease without bulky disease, with reduced clinical toxicity. Mitoxantrone containing regimen was not found to have an equivalent efficacy and clinical toxicity was most frequent and severe. We felt that mitoxantrone could be consider a second-line drug in the treatment of advanced Hodgkin's disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Epirubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Mitoxantrona/uso terapêutico , Análise Atuarial , Adolescente , Adulto , Agranulocitose/induzido quimicamente , Bleomicina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dacarbazina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/efeitos adversos , Estudos Prospectivos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Vimblastina/administração & dosagemRESUMO
The outcome of treatment for a first relapse in early stages (IA and IIA) of Hodgkin's disease after primary radiotherapy was analyzed in 86 patients. They received total nodal radiotherapy (TNR) as the primary treatment. Survival was used as the major endpoint. Median follow-up was 13.1 years. Duration of first complete remission was 60% for patients in stage IA and 39% for patients in stage IIA (p < .01). At 10-years, the survival for patients in stage IA was 78% and only 55% for patients in stage IIA (p < .01). A risk factor analysis showed that the presence of stage IIA and bulky disease (adenopathy > 7 cm) were associated with a worse prognosis. We believe that the use of TNR as initial treatment in early stages of Hodgkin's disease should be considered in patients in stage IA and without bulky disease. Patients in stage IIA and risk factors, such as bulky disease, should be treated with more aggressive therapeutic regimens.
Assuntos
Doença de Hodgkin/radioterapia , Irradiação Linfática , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Tábuas de Vida , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Vimblastina , Vincristina/administração & dosagemRESUMO
Beta 2 microglobulin is a low molecular weight protein found on the surface of all nucleated cells: it is the light chain of the HL-A histocompatibility complex. The increased levels of serum beta 2 microglobulin in patients with multiple myeloma have been associated with a poor prognosis. Pretreatment levels of serum beta 2 microglobulin were estimated in 70 previously untreated patients with multiple myeloma. In a multivariate analysis, serum beta 2 microglobulin levels and stage were the most significant prognostic factors for survival independent of other risk factors associated with a worse prognosis. There was a clear difference in survival duration observed between the patients with a high pretreatment level of beta 2 microglobulin and stage III (none alive at 5 years) compared with patients with normal levels and stage I (80% alive at five years) (p less than .001). We conclude that pretreatment-beta 2 microglobulin level is one of the most useful prognostic factors in patients with multiple myeloma.