Update on biochemical modulation of chemotherapeutic agents

Application of biochemical modulation strategies in the clinic has been hampered by many factors, particularly the problem of selectivity. Since modulation strategies rarely exploit biochemical pathways that are unique to tumor cells, increased toxicity to normal tissues may occur. The combination of 5-FU with leucovorin, PALA, or interferon appears to produce response rates in the range of 30% to 40% in patients with advanced colorectal cancer, but only 5-FU plus leucovorin has been shown to be superior to 5-FU alone. Biochemical modulation of cytarabine by hydroxyurea or fludarabine has produced encouraging results in patients with refractory non-Hodgkin's lymphoma and acute leukemia. Further studies are necessary to determine the value of this approach.