Study of Pegylated Liposomal Doxorubicin in First Line Therapy of Aggressive Lymphomas.

Purpose: Conventional doxorubicin is currently used in many treatment protocols for lymphoma. Pegylated liposomal doxorubicin has a different pharmacokinetic profile with prolonged half life, reduced toxicity, especially cardiotoxicity and possible enhanced antitumor activity. This study was designed to evaluate tolerability and efficacy of pegylated liposomal doxorubicin in patients with aggressive lymphomas.

Methods: Twenty-nine patients entered the study, 12 male, aged 36–86 (median 66 years), 22 with newly diagnosed CD20 positive diffuse large B-cell lymphoma (DLBCL), elderly with median age 77 years, 4 MALT in transformation, 2 mantle and one anaplastic. Patients’ characteristics: IPI-1 10%, IPI-2 25%, IPI-3 10%, IPI-4 55%, stages III–IV 60%, bulky disease 40%, extranodal 55%. Combined immunochemotherapy with Rituximab 375 mg/m², day1, added to standard CHOP was performed, 8 courses, with a follow up of nearly 3 years. Pegylated liposomal doxorubicin (Caelyx^®) replaced doxorubicin at 30 mg/m². Response was evaluated after 3 and 8 courses. Cardiac function was estimated at the beginning and after the end of therapy. LVEF, fractional shortening (FS) and myocardial performance index (MPI) according Tei et al, as most sensitive index for global LV function, were measured.

Results: All responded except for three, one with active SEL and one with CNS lymphoma (refractory 10%). Overall response 91%, CR 76%, PR 15%, overall survival 82%, relapse rate 4.5% (1/22). No synergistic toxicity was observed, as there were no remarkable hematological or extrahematological toxic events. No clinical deterioration of cardiac function was observed. The patient with anaplastic lymphoma had severe preexisting cardiovascular disease and died from cardiac complications, in lymphoma remission. Two patients experienced a single episode of atrial fibrillation with successful pharmaceutical conversion. None developed alopecia, nausea, vomiting, palmar-plantar erythrodysesthesia, local injury in extravasation area. Treatment related mortality was documented in none. LVEF and FS were not changed, but MPI was slightly increased, detecting subclinical myocardial dysfunction.

Conclusions: Pegylated liposomal doxorubicin is useful in the treatment of aggressive lymphomas, including elderly patients, well tolerated, producing durable complete remissions and offering advantages in combination with immunotherapy.