Phase II Study of RCHOP with Pegylated Liposomal Doxorubicin (DRCOP) for Patients > 60 Years Old with Untreated Diffuse Large B Cell Lymphoma (DLBCL).

Abstract

Background: DLBCL is a common lymphoma of older adults, and a potentially curable disorder with the regimen RCHOP (Coiffier, et.al. NEJM,2002). Doxorubicin, a key drug in the regimen, has risk for cardiotoxicity, and thus of concern in older patients (pts) with higher incidence of cardiovascular (CV) disease. In breast cancer pts pegylated liposomal doxorubicin (D) has shown greater cardiac safety and similar efficacy to doxorubicin. We thus replaced doxorubicin with D in RCHOP (DRCOP).Methods: The regimen is: Rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1–5. Eligibility criteria are: > 60 years of age; untreated confirmed DLBCL (no discordant histology); Ann Arbor stage II-IV; baseline LVEF 50%. CV disease is permitted, if symptoms controlled, but consult at baseline by Cardiologist and at follow-up required. Growth factor support recommended (not required).Results: 34 pts are evaluable for toxicity; 30 evaluable for response (1 pt off study after 1 cycle; 3 too early for response). Characteristics of pts: age 62–92 (median 75); 18 female; IPI 1=1pt; IPI 2 = 2 pts; IPI 3 = 16 pts; IPI >3 = 15 pts. Responses are: 28/30 (93%) CR; 2/30 (7%) PR. At this time, 3/30 failed: 1 progression; 1 death due to non-neutropenic pneumonia; 1 death due to disease. Grade 3–4 adverse events were: 1 drop in LVEF; 8 atrial arrhythmias (reversed); 1 hypotension (reversed); 1 chest pain (reversed); 17 neutropenia (13 febrile, with 5 infections); 3 hand-foot syndrome; 4 fatigue; 2 DVT; 2 neuropathy.Conclusions: DRCOP has a high CR rate in this study of older pts with DLBCL, despite intermediate/high risk IPI. We've noted only one case of low LVEF ; more common are atrial arrythmias (8 pts), reversible. Neutropenia is the most common grade 3–4 adverse event (17 pts), and thus we strongly recommend growth factor support.