The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy

Abstract

Determinants of Response to Fluopopyrimidines in Combination with CF.- Overview: Rational Basis for Development of Fluoropyrimidine/5-Formyltetrahydrofolate Combination Chemotherapy.- The Natural and Unnatural Diastereomers of Leucovorin: Aspects of Their Cellular Pharmacology.- Distribution and Metabolism of Calcium Leucovorin in Normal and Tumor Tissue.- Pole of Dose, Schedule and Route of Administration of 5-Formyltetrahydrofolate: Preclinical and Clinical Investigations.- Pharmacokinetic Analysis of (6S)-5-Formyltetrahydrofolate (1-CF), (6R)-5-Formyltetrahydrofolate (d-CF) and 5-Methyltetrahydrofolate (5-CH3-THF) in Patients Receiving Constant i. v. Infusion of High-Dose (6R,S)-5-Formyltetrahydrofolate (Leucovorin).- Evidence for Thymidylate Synthase as the Critical Site of Action of Fluoropyrimidines in Combination with CF.- The Role of Thymidylate Synthase in the Response to Fluoropyrimidine-Folinic Acid Combinations.- Tumor Cell Responses to Inhibition of Thymidylate Synthase.- Selectivity of CF and 5-Fluorouracil: Critical Role of Polyglutamylation.- Methods for Thymidylate Synthase Pharmacodynamics: Serial Biopsy, Free and Total TS, FdUMP and dUMP, and H4PteGlu and CH2-H4PteGlu Assays.- The Treatment of Metastatic Breast Cancer with 5-Fluorouracil and Leucovorin.- Thymidylate Synthase and Fluorouracil.- Mechanisms for Cisplatin-FUra Synergism and Cisplatin Resistance in Human Ovarian Carcinoma Cells both In Vitro and In Vivo.- Summation of Sessions 1 and.- Summation of Session 1.- Summation of Session 2.- Therapeutic Efficacy and Toxicity of Fluoropypimidines in Combination with CF.- The Roswell Park Memorial Institute and Gastrointestinal Tumor Study Group Phase III Experience with the Modulation of 5-Fluorouracil by Leucovorin in Metastatic Colorectal Adenocarcinoma.- Mount Sinai Clinical Experience with Leucovorin and 5-Fluorouracil.- High-Dose Weekly Oral Leucovorin and 5-Fluorouracil in Previously Untreated Patients with Advanced Colorectal Carcinoma: A Phase I Study.- A Controlled Clinical Trial Including Folinic Acid at Two Distinct Dose Levels in Combination with 5-Fluorouracil (5FU) for the Treatment of Advanced Colorectal Cancer: Experience of the Mayo Clinic and North Central Cancer Treatment Group.- 5-Fluorouracil (FUra) and Folinic Acid (FA) Therapy in Patients with Colorectal Cancer.- A Northern California Oncology Group Randomized Trial of Single Agent 5-FU vs. High-Dose Folinic Acid + 5-FU vs. Methotrexate + 5-FU + Folinic Acid in Patients with Disseminated Measurable Large Bowel Cancer.- Clinical Experience with CF-FUra.- A Randomized Trial of 5-Fluorouracil Alone versus 5-Fluorouracil and High Dose Leucovorin in Untreated Advanced Colorectal Cancer Patients.- Pharmacodynamics of 5-Fluorouracil and Leucovorin.- 5-Fluorouracil and 5-Formyltetrahydrofolate in Advanced Malignancies.- Folinic Acid (CF)/5-Fluorouracil (FUra) Combinations in Advanced Gastrointestinal Carcinomas.- Fffective Salvage Therapy for Refractory Disseminated Breast Cancer with 5-Fluorouracil and High-Dose Continuous Infusion Folinic Acid.- Progress Report on a Phase II Trial of 5-Fluorouracil Plus Citrovorum Factor in Women with Metastatic Breast Cancer.- Adjuvant Therapy for Colorectal Cancer: The NSABP Clinical Trials.- Chemotherapy of Advanced and Relapsed Squamous Cell Cancer of the Head and Neck with Split-Dose Cisplatinum (DDP), 5-Fluorouracil (Fura) and Leucovorin (CF).- 5-Fluorouracil/Folinic Acid/Cisplatin-Combination and Simultaneous Accelerated Split-Course Radiotherapy in Advanced Head and Neck Cancer.- Progress Report on Studies of FAM-CF for Gastric Cancer and Intra-peritoneal Administration of FUra-CF Followed by Cisplatin (DDP).- Clinical Experience with 5-FU/DDP +- OHDW Combination Chemotherapy in Patients with Advanced Colorectal Carcinoma.- 5-Fluorouracil and Folinic Acid: Summary of Clinical Experience.- Panel Discussion of Future Directions.- Abbreviations.- Author Index.