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Single Agent Chemotherapeutic Agents

Leukemia Insights - Spring 2010

Phase II study of bendamustine

Bendamustine is a rationally designed alkylating agent structurally resembling chlorambucil and cyclophosphamide [Gandhi V, Clin Cancer Research 2009 15:7456]. It has received FDA approval for the treatment of chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. A phase I trial of bendamustine administered intravenously twice daily (fractionated similar to the cyclophosphamide dosing for hyper-CVAD) for 8 doses was conducted. The MTD was determined to be 75 mg/m2 with further dose escalation predominantly limited by reversible mild to moderate nephrotoxicity [Rios M, Blood 2009 114:Abstract 4156]. Preliminary activity was encouraging with cytoreductions in peripheral and marrow blasts noted in several heavily pretreated subjects. The phase II portion of the trial is actively recruiting.

Phase I study of 4’-Thio-ara-C (triarabine)

4’-Thio-ara-C (triarabine) is a novel deoxycytidine nucleoside analog that is structurally related to cytarabine, differing only by substitution of a sulfur atom in place of the oxygen in the arabinose sugar ring. Triarabine requires conversion to the active triphosphate by intracellular kinases after which it competes with deoxycytidine triphosphate for incorporation into DNA, ultimately resulting in cell death. This dose escalation study will evaluate two schedules of triarabine given intravenously daily over 1 hour for either three or five days. Concurrent treatment for active CNS disease is permitted. Accrual is planned within the upcoming months.

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