Fluoropyrimidines In Cancer Therapy (cancer Drug Discovery And Development)

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. Front Matter....Pages i-xii Relative Role of 5-Fluorouracil Activation and Inactivation Pathways on Its Cytotoxic Effects....Pages 1-27 Dihydropyrimidine Dehydrogenase and Treatment by Fluoropyrimidines....Pages 29-36 Biochemical Bases of the 5-Fluorouracil—Folinic Acid Interaction and of its Limitations....Pages 37-66 Molecular Mechanisms Regulating the Expression of Thymidylate Synthase....Pages 67-82 Regulation of Thymidylate Synthase Gene Expression and Drug Response....Pages 83-91 Death Receptor Signaling in the Mechanism of 5-Fluorouracil Action....Pages 93-105 Circadian Rhythms in 5-Fluorouracil Pharmacology and Therapeutic Applications....Pages 107-128 Relevance of Scheduling to the Efficacy of 5-Fluorouracil Alone and in Combination with Other Agents....Pages 129-138 Noninvasive Studies of Fluoropyrimidines....Pages 139-152 Comparative Antitumor Activity of 5-Fluorouracil (5-FU) Prodrugs in Preclinical Model Systems....Pages 153-162 Bimonthly 48-h Leucovorin and 5-Fluorouracil-Based Regimens in Advanced Colorectal Cancer....Pages 163-173 Review on the Combination of Systemic and Locoregional Treatment for Colorectal Liver Metastases....Pages 175-182 Fluoropyrimidines in Advanced Colorectal Cancer....Pages 183-190 The Mayo/NCCTG Experience with 5-Fluorouracil and Leucovorin in Adjuvant Advanced Colorectal Cancer....Pages 191-198 Fluoropyrimidines for the Adjuvant Treatment of Colorectal Cancer....Pages 199-208 Clinical Trials of UFT Leucovorin in Gastrointestinal Malignancies....Pages 209-218 The Development of Oral UFT with and without Leucovorin....Pages 219-228 UFT in Elderly Patients with Colorectal Cancer....Pages 229-234 Clinical Trials of the Eniluracil/5-Fluorouracil Combination....Pages 235-247 Discovery and Preclinical Pharmacology of Capecitabine....Pages 249-259 Capecitabine, A Tumor-Targeting Oral Fluoropyrimidine....Pages 261-273 Capecitabine....Pages 275-284 Preclinical and Clinical Practice of S-1 in Japan....Pages 285-302 Preclinical and Clinical Practice of Low-Dose FP Therapy in Japan....Pages 303-318 Back Matter....Pages 319-325

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.

5-Fluorouracil (5-FU) is an analog of uracil (Fig. I) but, owing to its additional resemblance to orotic acid and thymine, the drug uses the same pathways as these natural substrates.