, Volume 18, Issue 4, pp 315-329

Conceptual Changes in Cancer Chemotherapy: From an Oral Fluoropyrimidine Prodrug, UFT, to a Novel Oral Fluoropyrimidine Prodrug, S-1, and Low-Dose FP Therapy in Japan

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The conventional concept in cancer chemotherapyconsiders that no efficacy can be attained withoutprovoking adverse reactions. We presented concretedescriptions based on a novel concept allowing us toemerge from the old one. Relief of adverse reactions,e.g., diarrhea, stomatitis, anorexia, and H&Fsyndrome, not only improves QOL of the patient butalso allows prolongation of the treatment periodwithout lowering patient compliance.

We describe in this paper a therapeutic modality which is basedon SRC (self-rescuing concept)featuring dual activity, i.e., effect-enhancingactivity and adverse reaction-reducing activity.

We present the theory and practice of S-1, anovel oral fluoropyrimidine anticancer agent designedto enhance anticancer activity and reducegastrointestinal toxicity through the deliberatecombination of the following components: an oralfluoropyrimidine agent tegafur; a DPD inhibitor (CDHP)which is more potent than uracil used in UFT; and anORTC inhibitor (Oxo) which localizes in thegastrointestinal tract. Furthermore, we refer tocombination therapy with 5-FU (CIV) and low-doseconsecutive CDDP in which CDDP was used as a modulatorof 5-FU and to the theory and practice of combinationtherapy with 5-FU (CVI) intermittent (Monday,Wednesday, and Friday) administration and low-doseCDDP consecutive administration in which a differencein cell cycle between gastrointestinal mucosal celland tumor cell or between bone marrow cell and tumorcell was utilized. We intend in future to combinethe abovementioned therapeutic modalities provokingless adverse reactions and being gentle to patientswith cancer in an effort to further increase theirlife expectancy.