Peter J. O'dwyer, MD

The combination of irinotecan and fluorouracil (5-FU) is synergistic when applied to human colon cancer cell lines in vitro and appears to be schedule-dependent: maximal activity occurs when irinotecan is administered prior to 5-FU. In this phase I study, irinotecan is administered in combination with UFT and leucovorin in patients with advanced solid tumors.

Drs. Takimoto and Allegra present a comprehensive overview of the development of antifolates over the past decade and a half. The antifolates are antimetabolite antineoplastic agents that are structurally and chemically similar to naturally occurring folates required for the synthesis of purines and pyrimidines. These drugs interfere with DNA synthesis by inhibiting key enzymes. They are transported across the plasma membrane and converted intracellularly to cytotoxic species, which must compete with endogenous substrates for target enzyme binding.