期刊
LEUKEMIA & LYMPHOMA
卷 58, 期 10, 页码 2310-2318出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2017.1298751
关键词
Histone deacetylase inhibitor; multiple myeloma; lymphoma; phase 1; pharmacokinetics
资金
- National Cancer Institute [U01CA076576, T32CA165998, R21CA156222]
- NATIONAL CANCER INSTITUTE [K12CA133250, R21CA156222, P30CA016058, T32CA165998, U01CA076576, UM1CA186712] Funding Source: NIH RePORTER
Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval in multiple myeloma (MM) and T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, in a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, and the MTD was defined as 40mg dosed three times weekly for three weeks of a 28-day cycle. One patient each with MM and mantle cell lymphoma demonstrated disease control for 19 and 27 months (ongoing), respectively. Treatment was associated with reduction of serum CD44, a transmembrane glycoprotein associated with steroid and immunomodulatory drug resistance in MM. Our findings indicate that AR-42 is safe and that further investigation of AR-42 in combination regimens for the treatment of patients with lymphoma and MM is warranted.
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