期刊
BLOOD
卷 105, 期 8, 页码 3058-3065出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-07-2911
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- NCI NIH HHS [R01 CA102278, P30-CA16086] Funding Source: Medline
- NCRR NIH HHS [RR00046] Funding Source: Medline
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/m(2) and PegLD on day 4 at 30 mg/m(2) to 42 patients with advanced hematologic malignancies. Grade 3 or 4 toxicities in at least 10% of patients included thrombocytopenia, lymphopenia, neutropenia, fa-tigue, pneumonia, peripheral neuropathy, febrile neutropenia, and diarrhea. The MTD based on cycle 1 was 1.50 and 30 mg/m(2) of bortezomib and PegLD, respectively. However, due to frequent dose reductions and delays at this level, 11,30 and 30 mg/m(2) 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.(c) 2005 by The American Society of Hematology.
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