A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL

Background:Standard therapy for lymphoma consists of acyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP)combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternativeto doxorubicin for patients with lymphoma because of its more favorable safetyprofile and potentially more selective uptake in lymphoma. The objectives ofthis study were to determine the maximum tolerated dose (MTD) of liposomaldaunorubucin with CVP (COP-X) and the tolerability of the regimen in patientswith indolent lymphoma.Patients and methods:Patients with low-grade andintermediate-grade lymphoma having adequate cardiac, hepatic, and renalfunction were enrolled. Patients received C 750 mg/m², V 1.4mg/m² (maximum 2.0 mg), and liposomal daunorubicin 50–100mg/m² i.v. on day 1 and P 100 mg p.o. on days 1–5. MTD wasthe liposomal daunorubicin dose associated with 20% dose-limitingtoxicity (ANC <500/mm³ for >5 days or febrile neutropenia).Results:Twenty patients, median age 59 years, were treated. Theliposomal daunorubicin MTD combined with CVP was 70–80 mg/m²,depending on patient population. No significant non-hematologic toxicityoccurred. Response rate was 44% (2 complete and 5 partial responses).Conclusions:A liposomal daunorubicin dose of 80 mg/m²in the COP-X regimen was well tolerated with little non-hematologic toxicity.