Randomized Comparison of ACVBP and m-BACOD in the Treatment of Patients With Low-Risk Aggressive Lymphoma: The LNH87-1 Study

Tilly, Hervé; Mounier, Nicolas; Léderlin, P.; Brière, Josette; Dupriez, Brigitte; Sebban, Catherine; Bosly, André; Biron, Pierre; Nouvel, C.; Herbrecht, Raoul; Bron, Dominique

doi:10.1200/jco.2000.18.6.1309

Cited by 55 publications

(26 citation statements)

References 30 publications

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“…This justifies a close monitoring of patients treated with ACVBP in the early phase of the treatment, especially those with an initial poor performance status or those older than 65 years of age. As toxicity is strongly reduced in patients younger than 60 years of age, [9][10][11][12] it is reasonable to assume that the advantage of ACVBP over standard CHOP should be confirmed in this population.…”

Section: Acvbp Vs Chop For Poor-prognosis Aggressive Nhl 4287mentioning

confidence: 99%

“…9,10 In a previous study, the comparison of this regimen with m-BACOD (cyclophosphamide, doxorubicin, vincristine, bleomycin, methotrexate, and dexamethasone), a third-generation regimen, in patients with low-risk aggressive lymphoma, showed that ACVBP could be beneficial for patients with more advanced disease. 11 Therefore, in 1993, the GELA initiated a phase 3 study comparing ACVBP to CHOP in patients with poor-prognosis aggressive lymphoma. We restricted this trial to patients aged between 61 and 69 years because another study from our group had shown that patients younger than 60 years of age with poor-risk aggressive lymphoma could benefit from consolidative high-dose therapy with stem cell rescue in the front-line regimen.…”

Section: Introductionmentioning

confidence: 99%

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Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma

Tilly¹

2003

Blood

288

171

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We conducted a randomized trial to compare the intensive conventional chemotherapy regimen ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with poor-risk aggressive lymphoma. Patients aged 61 to 69 years who had aggressive non-Hodgkin lymphoma with at least one prognostic factor of the age-adjusted international prognostic index (IPI) were included. ACVBP consisted of an induction phase of intensified chemotherapy and central nervous system (CNS) prophylaxis followed by a sequential consolidation phase. Of the 708 patients registered for the study, 635 were eligible. The rate of complete response was 58% in the ACVBP group and 56% in the CHOP group (P ‫؍‬ .5). Treatmentrelated death occurred in 13% of the ACVBP group and 7% of the CHOP group (P ‫؍‬ .014). At 5 years, the event-free survival was 39% in the ACVBP group and 29% in the CHOP group (P ‫؍‬ .005). The overall survival was significantly longer for patients treated with ACVBP, at 5 years it was 46% compared with 38% for patients treated with CHOP (P ‫؍‬ .036). CNS progressions or relapses were more frequent in the CHOP group (P ‫؍‬ .004). Despite higher toxicity, the ACVBP regimen, used as first-line treatment for patients with poor-risk aggressive lymphoma, is superior to standard CHOP with regard to both event-free survival and overall survival. IntroductionThe incidence of non-Hodgkin lymphoma, especially that of aggressive histology, is steadily increasing. 1 However, during the last 30 years, improvement in treatment outcome remained modest 2 and less than 50% of the patients with aggressive lymphoma are cured.The standard treatment used since the 1970s is the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy regimen, 3 delivering 8 cycles at a 3-week interval in advanced disease. Subsequently, new combinations including additional non-cross-reacting drugs such as methotrexate, bleomycin, or cytarabine have been proposed. [4][5][6] However, multicenter randomized trials failed to demonstrate any survival advantage of these second-and third-generation regimens over the standard CHOP. 7,8 Since 1980, the Groupe d'Etudes des Lymphomes (GELA) has developed a chemotherapy schedule, the ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen, which consisted of an induction phase of 4 cycles of intensified CHOP with central nervous system (CNS) prophylaxis followed by a sequential consolidation phase. 9,10 In a previous study, the comparison of this regimen with m-BACOD (cyclophosphamide, doxorubicin, vincristine, bleomycin, methotrexate, and dexamethasone), a third-generation regimen, in patients with low-risk aggressive lymphoma, showed that ACVBP could be beneficial for patients with more advanced disease. 11 Therefore, in 1993, the GELA initiated a phase 3 study comparing ACVBP to CHOP in patients with poor-prognosis aggressive lymphoma. We restricted this trial to...

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Section: Acvbp Vs Chop For Poor-prognosis Aggressive Nhl 4287mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma

Tilly¹

2003

Blood

288

171

View full text Add to dashboard Cite

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“…[1][2] Although most DLBCL respond to modern chemotherapy regimens that include an anthracycline and alkylating agents, only half of the patients are alive and disease free at 5 years. [2][3][4][5] These results make the search of potential drug resistance mechanisms particularly important in DLBCL. Widely used prognostic factors (especially those utilized for the International Prognostic Index (IPI) 6 are essentially based on the patient's general condition, disease stage, and lactico deshydrogenase (LDH) serum levels but not on specific biological abnormalities present in DLBCL tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of GST-π expression in diffuse large B-cell lymphomas

et al. 2003

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Among mechanisms potentially involved in resistance to alkylating agents and anthracyclines, the glutathione system has been extensively studied in vitro. We analyzed by immunohistochemistry the relation between glutathione stransferase p (GST-p) expression in tumor cells and outcome in 69 cases of diffuse large B-cell NHL (DLBCL). GST-p expression was considered as low when o50% of tumor cells were stained and high when X50% tumor cells were stained. Median follow-up was 58 months. GST-p expression was correlated with the probability of achieving complete remission (CR). Patients with high GST-p expression had a worse 5-year freedom from progression (FFP). High GST-p expression was associated with a trend for lower survival. In the group of patients with International Prognostic Index (IPI) 0-1, low GST-p expression was associated with a CR rate of 88%, a 5-year FFP of 76720% and a 5-year survival of 78716% compared to 36, 14716 and 40732%, respectively, in patients with a high GST-p expression (P ¼ 0.002, Po10 À5 and P ¼ 0.01, respectively). No correlation was found between GST-p expression and lactico deshydrogenase serum level, age, Ann Arbor stage, performance status, and IPI index. Both GST-p expression and the IPI index correlated with FFP. After incorporating IPI and GST-p expression in a multivariate analysis for FFP, GST-p expression remained the only prognostic factor (P ¼ 0.003). Our findings suggest that GST-p expression had strong prognostic significance in DLBCL, which appears to be independent of other prognostic parameters in those disorders.

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“…This regimen was compared with conventional doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP), 16 which has shown benefit in event-free survival (EFS) over CHOP and methotrexate, bleomycin, cyclophosphamide, and etoposide regimens for patients with at least two adverse prognostic factors. 17,18 At the first interim analysis in September 1995, the trial was stopped because of the poor experimental arm results. 19 We report the final analysis of this trial with a median follow-up of 60 months.…”

Section: T O Improve the Cure Rate For Aggressive Non-mentioning

confidence: 99%

Shortened First-Line High-Dose Chemotherapy for Patients With Poor-Prognosis Aggressive Lymphoma

Gisselbrecht

Lepage

Molina

et al. 2002

JCO

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189

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for the Groupe d'Etude des Lymphomes de l'Adulte Purpose: Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT).Patients and Methods: Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT.Results: Eligible patients (n ‫؍‬ 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% ؎ 8% and 46% ؎ 8% (P ‫؍‬ .007) and 52 ؎ 8% and 39 ؎ 8% (P ‫؍‬ .01), respectively. Survival was independently affected by age greater than 40 years (P ‫؍‬ .0003), T-cell phenotype (P ‫؍‬ .009), bone marrow involvement (P ‫؍‬ .003), and HDT treatment group (P ‫؍‬ .04). Conclusion:Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received doseintensity before HDT was too low when compared with ACVBP and HDT and was given too early.

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Randomized Comparison of ACVBP and m-BACOD in the Treatment of Patients With Low-Risk Aggressive Lymphoma: The LNH87-1 Study

Cited by 55 publications

References 30 publications

Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma

Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma

Prognostic value of GST-π expression in diffuse large B-cell lymphomas

Shortened First-Line High-Dose Chemotherapy for Patients With Poor-Prognosis Aggressive Lymphoma

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