Etoposide and Teniposide

Etoposide and teniposide are epipodophyllotoxins that inhibit topoisomerase II, a ubiquitous enzyme that is essential for survival and that plays critical roles in DNA metabolism, chromosome organization, and mitosis (1). Etoposide and teniposide act by stabilizing the covalent linkage between DNA and topoisomerase II (1). These agents have been studied in clinical trials for over 25 yr (2, 3), but their contribution to the therapy of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in children remains to be clearly elucidated. There are minor distinctions between etoposide and teniposide. The latter agent is more potent in in vitro tests of cytotoxicity, is associated with higher albumin binding, is more lipophilic, and has a slightly longer plasma elimination halflife (approx 8 vs 6 h) (4–6). However, these differences do not correlate with any therapeutic advantage for teniposide over etoposide in vivo (7). Randomized studies have shown that teniposide and etoposide have similar levels of antitumor activity when used at equitoxic doses (8, 9), and current regimens for leukemia that utilize an epipodophyllotoxin employ etoposide. Hence, in this chapter, the two agents are discussed under the assumption that they are more or less interchangeable.