Abstract
Several new antimetabolites have been evaluated in clinical trials in recent years. Those with the most promising activity include the structurally related purine analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin. These compounds have shown impressive activity against a broad spectrum of indolent lymphoproliferative disorders, including hairy-cell leukemia, chronic lymphocytic leukemia, and low-grade non-Hodgkin's lymphomas. They may also be useful in the treatment of acute leukemias. In contrast, they lack activity against common solid tumors. They have been generally well tolerated in large clinical trials; however, each of them is myelosuppressive and immunosuppressive. It is unlikely that any one of these drugs, when used as a single agent, will provide optimal therapy for any disease other than, possibly, hairy-cell leukemia. Combinations with other cytotoxic agents and biologics are in development, and perhaps they will lead to more effective regimens in the future.
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