Combined therapy in the treatment of primary mediastinal B-cell lymphoma: conventional versus escalated chemotherapy

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/m2, vincristine 1.4 mg/m2, prednisone 40 mg/m2, epirubicin 70 mg/m2, and bleomycin 10 mg/m2) or mega CEOP-Bleo (cyclophosphamide 1000 mg/m2, epirubicin 120 mg/m2, 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% confidence interval (CI): 58% to 70%] for conventional arm vs 81% (95 CI: 77–86%) 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% (95% CI: 44–59%) compared to 70% (95% CI: 65–76%) in the intensive arm (p>0.01). OS rates were also different: 54% (95% CI: 48–57%) vs 70% (95% CI: 65–76%), 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.