RESUMO
BACKGROUND: The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. METHODS: We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. FINDINGS: One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). INTERPRETATION: Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable. FUNDING: Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.
Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prednisolona , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Medição de Risco , Rituximab , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento , Vincristina , Vindesina/administração & dosagem , Vindesina/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Diffuse large B-cell lymphoma is a common cancer in elderly patients. Although treatment has been standardised in younger patients, no prospective study has been done in patients over 80 years old. We aimed to investigate the efficacy and safety of a decreased dose of CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) chemotherapy with a conventional dose of rituximab in elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, multicentre, single-arm, phase 2 study of patients aged over 80 years who had diffuse large B-cell lymphoma. Patients were included from 38 centres in France and Belgium. All patients received six cycles of rituximab combined with low-dose CHOP (R-miniCHOP) at 3-week intervals. Patients received 375 mg/m(2) rituximab, 400 mg/m(2) cyclophosphamide, 25 mg/m(2) doxorubicin, and 1 mg vincristine on day 1 of each cycle, and 40 mg/m(2) prednisone on days 1-5. The primary endpoint was overall survival, both unadjusted and adjusted for treatment and baseline prognostic factors. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT01087424. FINDINGS: 150 patients were enrolled between Jan 9, 2006, and Jan 23, 2009 and 149 were included in the intention-to-treat analyses. Median age was 83 years (range 80-95). After a median follow-up of 20 months (range 0-45), the median overall survival was 29 months (95% CI 21 to upper limit not reached); 2-year overall survival was 59% (49-67%). In multivariate analyses, overall survival was only affected by a serum albumin concentration of 35 g/L or less (hazard ratio 3·2, 95% CI 1·4-7·1; p=0·0053). Median progression-free survival was 21 months (95% CI 13 to upper limit not reached), with a 2-year progression free survival of 47% (38-56). 58 deaths were reported, 33 of which were secondary to lymphoma progression. 12 deaths were attributed to toxicity of the treatment. The most frequent side-effect was haematological toxicity (grade ≥3 neutropenia in 59 patients; febrile neutropenia in 11 patients). INTERPRETATION: R-miniCHOP offers a good compromise between efficacy and safety in patients aged over 80 years old. R-miniCHOP should be considered as the new standard treatment in this subgroup of patients. FUNDING: Groupe d'Etude des Lymphomes de l'Adulte (GELA).
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso de 80 Anos ou mais , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bélgica , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , França , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Razão de Chances , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Rituximab , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
BACKGROUND: As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival. DESIGN AND METHODS: The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial. RESULTS: With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69-81) and 78% (CI: 72-83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494). CONCLUSIONS: In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Adolescente , Adulto , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Estudos de Casos e Controles , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Rituximab , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Vindesina/efeitos adversos , Vindesina/uso terapêutico , Adulto JovemRESUMO
The aim of this study was to evaluate the efficacy and toxicity of two chemotherapy regimens based on platinum and cytarabine in association with etoposide and methylprednisolone (ESHAP) or with dexamethasone (DHAP) with or without Rituximab (± R) in patients with refractory or a relapsed Primary Central Nervous System Lymphoma (PCNSL). All consecutive patients from two French centers with refractory or relapsed PCNSL treated with ESHAP/DHAP ± R were included. We analyzed the overall response rate (ORR), toxicity and overall survival (OS) after salvage chemotherapy. Intensive chemotherapy and hematopoietic stem cell rescue (IC + HCR) was offered to patients less than 65 years of age and consisted of high-dose thiotepa, busulfan and cyclophosphamide. These results were compared with two previously reported series of PCNSL patients treated with the CYVE (high-dose cytarabine and etoposide) regimen at relapse. Twenty-two patients received a total of 60 DHAP/ESHAP cycles (median 3; range 1-5). The median age was 59 years. The ORR after salvage chemotherapy was 59%. Toxicity was mainly hematological, 18% of patients showing febrile neutropenia. There was no treatment-related death. ESHAP or DHAP regimens led to similar ORRs compared to the CYVE regimen in relapsed or refractory PCNSL, although they seemed less toxic. The therapeutic results of the ESHAP/DHAP regimens in relapsed or refractory PCNSL were also similar to those for relapsed systemic non-Hodgkin's lymphomas (sNHL). Both chemotherapies, CYVE regimen and ESHAP/DHAP are treatment options to be considered in relapsed or refractory PCNSL, especially when IC + HCR is planned as a consolidation treatment. More efforts are still needed to improve the ORR at relapse.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Murinos/administração & dosagem , Bussulfano/administração & dosagem , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/patologia , Cisplatino/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma/mortalidade , Linfoma/patologia , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Rituximab , Tiotepa/administração & dosagem , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to compare the quality of life (QOL) of high-risk breast cancer patients included in a randomized clinical trial (PEGASE 01) comparing conventional chemotherapy versus adding an additional high-dose chemotherapy (HDC) cycle with blood stem cell support. METHODS: A total of 314 patients were included in the clinical trial. QOL evaluations were available for 199 patients. QOL was assessed over a 1-year follow-up period, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. The results were analyzed using a linear mixed-effects model. RESULTS: Toxicity of HDC has a strong negative impact on patients' QOL during the treatment phase. This negative impact tended to last longer in the HDC group, as for most of the QLQ-C30 scales, the QOL scores of HDC patients tend to improve at a slower rate than that of patients receiving standard chemotherapy. In particular, physical functioning remains deteriorated 1 year after inclusion for HDC patients comparatively to conventional chemotherapy patients (85.99 vs. 76.65, P = 0.021), and the pain score was still higher in the HDC group at that time (28.32 vs. 15.97, P = 0.004). CONCLUSION: HDC has a negative impact on QOL even after treatment phase. In the absence of an overall survival benefit of using HDC for high-risk breast cancer patients, QOL studies with a longer follow-up play an important role in informing the complex trade-off implied by HDC between higher toxicity, reduced risk of relapse, and QOL decrease after the active phase of treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Qualidade de Vida , Adulto , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do TratamentoRESUMO
PURPOSE: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584). PATIENTS AND METHODS: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age ≥ 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio ≥ 0.35, erythrocyte sedimentation rate (ESR) ≥ 50 without B-symptoms or ESR ≥ 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPPbaseline-IFRT (n = 255). RESULTS: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPbaseline-IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90%CI, -0.7%-8.8%) and of 1.1% (90%CI,-3.5%-5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP)baseline more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD). CONCLUSIONS: The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPPbaseline were more toxic than four or six cycles of ABVD.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Radioterapia/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Fatores de Risco , Análise de Sobrevida , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto JovemRESUMO
PURPOSE: To study the impact of high-dose therapy (HDT) with autologous stem-cell support in patients with symptomatic multiple myeloma (MM) between the ages of 55 and 65 years. PATIENTS AND METHODS: One hundred ninety patients between 55 and 65 years old who had newly diagnosed stage II or III MM were randomly assigned to receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and autologous blood stem-cell transplantation (using either melphalan alone 200 mg/m(2) intravenous [IV] or melphalan 140 mg/m(2) IV plus busulfan 16 mg/kg orally as pretransplantation cytoreduction). RESULTS: Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8 months in the HDT group compared with 47.6 months in the CCT group. A trend to better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not statistically different (P = .91). The period of time without symptoms, treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT patients than for the CCT patients (P = .03). CONCLUSION: With a median follow-up time of approximately 10 years, this randomized trial confirmed a benefit of HDT in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed MM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Fatores Etários , Idoso , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
The aim of our study was to evaluate the impact on time to progression (TTP) and overall survival (OS) of high-dose chemotherapy (HD-CT) over conventional CT in metastatic breast cancer patients. Between 09/92 and 12/96, 61 patients with chemosensitive metastatic breast cancer were randomised between HD-CT using the CMA regimen (Mitoxantrone, Cyclophosphamide, Melphalan) applied as consolidation (32 patients) or maintenance CT (29 patients). At randomisation, 13 patients were in complete response, 47 in partial response and one had stable disease. The median TTPs from randomisation were 6 and 12 months in the standard and intensive groups, respectively (P < 0.0056), with a relapse rate of 86.2% vs. 62.5% at 2 years, and 100% vs. 81.3% at 5 years. The median OS times were 19.3 and 44.1 months, with an OS rate of 13.8% vs. 36.8% at 5 years (P < 0.0294). The CMA regimen could prolong the TTP of patients with chemosensitive metastatic breast cancer. Further studies are needed to determine if this translates into an effect on OS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , França , Humanos , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Non-Hodgkin's lymphoma of the breast represents 0.04%-0.50% of malignant lesions of the mammary gland. In this article, we report a single institution's experience with this rare disease. MATERIALS AND METHODS: Between 1982 and 1997, 19 patients with breast lymphoma were diagnosed, treated, and followed at this institution. RESULTS: There were 18 female patients and 1 male patient. All but one were cases of aggressive B-cell lymphoma. Ann Arbor stages were IE (n=5), IIE (n=9), IIIE (n=2), and IV (n=3). International Prognosis Index scores were 0 (n=2), 1 (n=8), 2 (n=7), and 3 (n=2). According to the Wiseman and Liao classification established in 1972, 11 cases were primary lymphomas of the breast, and 8 cases were secondary involvement of the breast. Median survival time was 21.5 months (range, 5.1-114.7 months). The 5-year overall survival was 29%. Median event-free survival time was 8.3 months. The clinical, radiologic, and histologic patterns of presentation match previously published data, even if the response rates and the survival times seem disappointing, probably because of the initial treatment by tumorectomy or mastectomy for some patients. CONCLUSIONS: Systemic chemotherapy should be the mainstay of treatment. Based on our experience and a review of the literature, the use of Wiseman and Liao's classification is questionable. In fact, it fails to detect whether some lymphomas of the breast present a specific natural history and therefore require specific management. New clinical and histologic criteria are to be identified.
Assuntos
Neoplasias da Mama/terapia , Linfoma não Hodgkin/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama Masculina/mortalidade , Neoplasias da Mama Masculina/terapia , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the potential cost savings of using sequential high dose chemotherapy (HDC), with granulocyte colony-stimulating factor (filgrastim) and stem cell support, rather than single course administration of HDC with bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). PERSPECTIVE: French public hospital perspective. METHODS: Direct medical costs of sequential treatment, estimated on the basis of physical quantities of resources consumed by 95 patients with inflammatory breast cancer (IBC) included in a French pilot multicentric trial (PEGASE 02), were compared with those of historical control groups of patients treated with single course HDC, either with BMT (n = 27) or PBSCT (n = 14). Costs were evaluated in 1998 French francs (1 Euro = 6.55957 French francs). RESULTS: The total cost of sequential HDC was significantly lower than that for single course HDC both with BMT (-29%; 22,755 Euros vs 32,284 Euros; p < 0.001) or PBSCT (-16%; 22,755 Euros vs 27,209 Euros; p = 0.026). This was mainly due to a reduction in the length of hospitalisation in transplantation units. CONCLUSION: According to our results, economic arguments cannot be used against the widespread use of sequential HDC for patients with IBC. However, further economic evaluations based on overall and disease-free survivals alongside a randomised clinical trial are still needed to definitively establish the cost effectiveness of sequential administration of HDC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Neoplasias da Mama/tratamento farmacológico , Custos Diretos de Serviços/estatística & dados numéricos , Custos de Medicamentos/estatística & dados numéricos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/economia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/economia , Neoplasias da Mama/cirurgia , Terapia Combinada , Redução de Custos , Esquema de Medicação , Feminino , Filgrastim , França , Hospitais Públicos/economia , Humanos , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/economia , Proteínas RecombinantesRESUMO
PURPOSE: The prognosis of relapsing primary CNS lymphoma (PCNSL) is poor. We report the results of a prospective multicenter trial of intensive chemotherapy followed by autologous hematopoietic stem-cell rescue (IC + HCR) in immunocompetent adult patients with PCNSL or intraocular lymphoma (IOL) after failure of high-dose methotrexate-based treatment. PATIENTS AND METHODS: Salvage treatment consisted of two cycles of high-dose cytarabine and etoposide (CYVE). Intensive chemotherapy combined thiotepa, busulfan, and cyclophosphamide. Forty-three patients (median age, 52 years; range, 23 to 65 years) were included, with relapse (n = 22), refractory disease (n = 17), or a partial response to first-line treatment (n = 4). The response to CYVE was not assessable in three cases because of treatment-related death. Twenty patients (47%) were chemosensitive to CYVE: 15 of them proceeded to IC + HCR. IC + HCR was also administered to 12 patients who did not respond to CYVE. All but one of the 27 patients who underwent IC + HCR entered complete remission. RESULTS: With a median follow-up of 36 months, the median overall survival was 18.3 months in the overall population, and 58.6 months among patients who completed IC + HCR. The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation. CONCLUSION: IC + HCR is an effective treatment for refractory and recurrent PCNSL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Neoplasias Oculares/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Bussulfano/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Neoplasias Oculares/tratamento farmacológico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Taxa de Sobrevida , Tiotepa/administração & dosagemRESUMO
Between 1990 and 1996, we conducted a randomized trial in adults with newly diagnosed acute myeloid leukemia (AML) in order to compare relapse-free interval (RFI) after double induction (arm B), timed-sequential induction (arm C), or control "3 + 7" induction (arm A). Patients achieving complete remission (CR) after induction +/- salvage received the same consolidation chemotherapy, which included a dosage stratification according to patient's age (younger or older than 50 years). This long-term analysis was performed in 592 patients (arm A/B/C, 197/198/197 patients). Overall CR rate was 76% without differences between the 3 arms, even if a salvage course was less frequently needed in arm B. Treatment-related mortality, either during the induction or the postremission phase, was not significantly higher in arms B and C than in arm A. Among the 449 CR patients, 250 relapsed (arm A/B/C, 90/87/73 patients) without significant differences in RFI in arms B and C versus arm A (P = .39 and .15, by the Gray test). However, when analyzing the 345 patients younger than 50, RFI was significantly improved in younger patients receiving timed-sequential induction (P = .038 by the Gray test), while not in those receiving double induction. Event-free survival and overall survival were similar in the 3 randomization arms.