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Leading cancer researchers update and review the mechanisms of action and the therapeutic selectivity and efficacy of 5-FU with and without leucovorin and its prodrugs in the treatment of colorectal cancer. Among the combination agents considered are UFT/LV, 5-FU/EU, capecitabine (Xeloda), S-1, and a variety of thymidylate synthase inhibitors. The authors discuss the potential advantages and disadvantages of these varied drugs and their mode of administration. Based on historical results with these agents when used alone, they also present a rationale for their results when used in combination with other agents. Although the action of the standard chemotherapeutic agent for the treatment of advanced colorectal cancer (5-fluorouracil or 5-FU) was improved significantly by combining it with leucovorin (LV), the improved response rate was associated with significant side-effects in approximately thirty percent of patients. In Fluoropyrimidines in Cancer Therapy, leading cancer researchers update and review the mechanisms of action and the therapeutic selectivity and efficacy of 5-FU, with and without LV and its prodrugs, in the treatment of colorectal cancer. Among the combination agents considered are Orzel (UFT/LV), 5-FU/Eniluracil (5-FU/EU), capecitabine (Xeloda), S-1, and a variety of thymidylate synthase inhibitors. The authors discuss the potential advantages and disadvantages of these varied drugs and their mode of administration. Based on the historical results with these agents when used alone, they also present a rationale for their results when used in combination with other agents.
Authoritative and integrative, Fluoropyrimidines in Cancer Therapy summarizes the latest preclinical and clinical experiences using fluoropyrimidines to treat colorectal cancer, delineates the underlying mechanisms and choices for therapy, describes the ongoing search to identify ever more effective and selective agents with novel mechanisms of action, and details the development of new mechanism-based combination therapies.
List of contents
1 Relative Role of 5-Fluorouracil Activation and Inactivation Pathways on its Cytotoxic Effects: Preclinical and Clinical Modulation.- 2 Dihydropyrimidine Dehydrogenase and Treatment by Fluoropyrimidines: Past and Future Directions.- 3 Biochemical Bases of the 5-Fluorouracil-Folinic Acid Interaction and of its Limitations: A Retrospective Analysis.- 4 Molecular Mechanisms Regulating the Expression of Thymidylate Synthase.- 5 Regulation of Thymidylate Synthase Gene Expression and Drug Response: Posttranscriptional Regulation and Cell Population Density.- 6 Death Receptor Signaling in the Mechanism of 5-Fluorouracil Action.- 7 Circadian Rhythms in 5-Fluorouracil Pharmacology and Therapeutic Applications.- 8 Relevance of Scheduling to the Efficacy of 5-Fluorouracil Alone and in Combination with Other Agents.- 9 Noninvasive Studies of Fluoropyrimidines.- 10 Comparative Antitumor Activity of 5-Fluorouracil (5-FU) Prodrugs in Preclinical Model Systems: Role of Leucovorin and Dihydropyrimidine Dehydrogenase Inhibitors.- 11 Bimonthly 48-h Leucovorin and 5-Fluorouracil-Based Regimens in Advanced Colorectal Cancer.- 12 Review on the Combination of Systemic and Locoregional Treatment for Colorectal Liver Metastases.- 13 Fluoropyrimidines in Advanced Colorectal Cancer: A Review of Six Consecutive Meta-Analyses.- 14 The Mayo/NCCTG Experience with 5-Fluorouracil and Leucovorin in Adjuvant Advanced Colorectal Cancer.- 15 Fluoropyrimidines for the Adjuvant Treatment of Colorectal Cancer: The NSABP Experience.- 16 Clinical Trials of UFT Leucovorin in Gastrointestinal Malignancies.- 17 The Development of Oral UFT with and without Leucovorin.- 18 UFT in Elderly Patients with Colorectal Cancer.- 19 Clinical Trials of the Eniluracil/5-Fluorouracil Combination.- 20 Discovery andPreclinical Pharmacology of Capecitabine.- 21 Capecitabine, A Tumor-Targeting Oral Fluoropyrimidine: Molecular Rationale and Clinical Validation.- 22 Capecitabine: A Rationally Developed Anticancer Drug.- 23 Preclinical and Clinical Practice of S-1 in Japan.- 24 Preclinical and Clinical Practice of Low-Dose FP Therapy in Japan: Japanese Use of Low-Dose FP Therapy.
Summary
Leading cancer researchers update and review the mechanisms of action and the therapeutic selectivity and efficacy of 5-FU with and without leucovorin and its prodrugs in the treatment of colorectal cancer. Among the combination agents considered are UFT/LV, 5-FU/EU, capecitabine (Xeloda), S-1, and a variety of thymidylate synthase inhibitors. The authors discuss the potential advantages and disadvantages of these varied drugs and their mode of administration. Based on historical results with these agents when used alone, they also present a rationale for their results when used in combination with other agents.
