Journal of Clinical Oncology, Vol 6, 351-379, Copyright © 1988 by American Society of Clinical Oncology
Teniposide in the treatment of leukemia: a case study of conflicting priorities in the development of drugs for fatal diseases
JL Grem, DF Hoth, B Leyland-Jones, SA King, RS Ungerleider and RE Wittes
Investigational Drug Branch, National Cancer Institute, Bethesda, MD 20892.
Teniposide, a semisynthetic epipodophyllotoxin, was found to be highly
active against murine leukemias, and the combination of teniposide with
cytosine arabinoside (ara-C) was curative in murine leukemia models. The
antitumor activity in preclinical models prompted introduction of
teniposide into the clinic in 1971. Although teniposide as a single agent
rarely produced a complete remission in heavily pretreated leukemia
patients, teniposide plus ara-C produced complete remissions in some
patients with refractory and relapsed acute lymphoblastic leukemia (ALL).
Innovative front-line and salvage regimens using teniposide have been
developed that incorporate a multi-drug strategy with early
intensification, rotation of drug combinations in maintenance, and regional
therapy in an effort to improve the cure rate in leukemia. However, as the
complexity of these regimens increases, the contribution of an individual
component such as teniposide becomes less clear. Although some of these
regimens for newly diagnosed and relapsed ALL are now thought to represent
the best available therapy, teniposide remains an investigational agent. In
this review, we outline and discuss the conflicts arising from the need to
answer drug-specific issues, and, at the same time, facilitate the
implementation of innovative, curative regimens.
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