Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the 
antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought 
to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of 
bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on 
days 1, 4, 8, and 11 from 0.90 to 1.50 mg/m2 and PegLD on day 4 at 30 mg/m2 to 
42 patients with advanced hematologic malignancies. Grade 3 or 4 toxicities in 
at least 10% of patients included thrombocytopenia, lymphopenia, neutropenia, 
fatigue, pneumonia, peripheral neuropathy, febrile neutropenia, and diarrhea. 
The MTD based on cycle 1 was 1.50 and 30 mg/m2 of bortezomib and PegLD, 
respectively. However, due to frequent dose reductions and delays at this level, 
1.30 and 30 mg/m2 are recommended for further study. Pharmacokinetic and 
pharmacodynamic studies did not find significant drug interactions between these 
agents. Antitumor activity was seen against multiple myeloma, with 8 of 22 
evaluable patients having a complete response (CR) or near-CR, including several 
with anthracycline-refractory disease, and another 8 having partial responses 
(PRs). One patient with relapsed/refractory T-cell non-Hodgkin lymphoma (NHL) 
achieved a CR, whereas 2 patients each with acute myeloid leukemia and B-cell 
NHL had PRs. Bortezomib/PegLD was safely administered in this study with 
promising antitumor activity, supporting further testing of this regimen.