[Biochemical modulation--the historical background]

Biochemical modulation is a word to mean biochemical or pharmacological modulation of the efficacy or side effects of a anticancer drug. Historically, combination therapy of methotrexate (MTX) and 5-fluorouracil (5-FU) developed by Bertino et al. in 1970s has been proved to be effective to advanced gastric cancer. Many combination therapies from 1960s seem to be based on this concept of biochemical modulation. Beside MTX and 5-FU combination, currently combined use of 5-FU or other fluoropyrimidines with cisplatin (CDDP) has been studied for the treatment of cancer of the digestive organs. The therapeutic efficacies in these combination of drugs were also found to be based on biochemical or pharmacological modulation of anticancer drugs.