Pegylated Liposomal Doxorubicin Replacing Conventional Doxorubicin in Standard R-CHOP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma: An Open Label, Single Arm, Phase II Trial

This phase II trial evaluated pegylated liposomal doxorubicin instead of doxdrubicin in standard R-CHOP therapy for elderly patients with diffuse large B-cell lymphoma. Of 79 eligible patients, the overall and complete response rates were 86% and 78%, respectively. Cardiac events greater than grade 3 were identified in 3 patients (4%). This regimen represents an effective strategy in this elderly population. Background: The present multicenter phase II trial evaluated the safety and efficacy of pegylated liposomal doxorubicin (PLD) instead of conventional doxorubicin in standard R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) therapy for elderly patients with diffuse large B-cell lymphoma. Materials and Methods: Patients aged > 60 years who had stage II to IV disease were included. Treatment consisted of rituximab 375 mg/m2 intravenously (I.V.); cyclophosphamide 750 mg/m2 IV; PLD 40 mg/m2 (maximum, 90 mg) I.V. over 1 hour; and vincristine 2.0 mg I.V., all on day 1. Additionally prednisone, 40 mg/m2, was given orally on days 1 to 1 to 5 (DRCOP [rituximab, cyclophosphamide, PLD, vincristine, and prednisone]). The cycles were repeated every 3 weeks for 6 to 8 cycles. Results: Eighty patients were enrolled and were evaluable for toxicity. The median age was 69 years. All except 1 had additional cardiac risk factors for anthracycline-induced cardiac toxicity beyond advanced age. From the intent-to-treat analysis of 79 eligible patients, the overall response rate was 86%, and the complete response rate was 78%. Cardiac events greater than grade 3 were identified in 3 patients (4%); grade 1 to 2 events, mostly asymptomatic declines in ejection fraction, were noted in another 16 patients. One death was attributed to cardiac failure. The estimated 5-year event-free and overall survival rate was 52% and 70%, respectively. Conclusion: DRCOP represents an effective strategy for potentially mitigating cardiotoxicity in elderly patients with aggressive B-cell lymphoma. Future studies incorporating baseline cardiac risk assessments, long-term follow-up data, and biospecimen collection for correlative science should be undertaken.