Clinical trials of teniposide (VM-26) in childhood acute lymphocytic leukemia

We describe the development of VM-26 (teniposide) as an effective agent in combination chemotherapy for childhood acute lymphocytic leukemia (ALL). Beginning with its paired use with cytarabine for patients relapsing on conventional therapy, teniposide has shown consistent ability to reduce leukemic cell populations not responsive to other agents. Encouraging results in the treatment of refractory ALL led to the decision to incorporate teniposide into combination chemotherapy for patients with newly diagnosed leukemia. This strategy has yielded higher cure rates for subsets of patients at high risk of treatment failure, including those with initial leukocyte counts of more than 100 x 10(9)/L, and may extend remission lengths for all patients, regardless of risk status. In view of the prolonged marrow aplasia seen with use of teniposide and cytarabine as inducing agents, the optimal role of this combination may be that of "remission reinforcement" therapy. Because of its novel mechanism of action, teniposide affords opportunities to develop new drug combinations that may increase the proportion of long-term ALL survivors still further.