The Expanding Role Of Folates And Fluoropyrimidines In Cancer Chemotherapy (advances In Experimental Medicine And Biology)

These proceedings discuss the biochemical, pharmacological and molecular determinants of response to FUra in combination with CF, and identifies conditions for optimal modulation of FUra activity. Also updates and reviews the response rate and response duration of patients treated with this combination, and defines future directions for patients with advanced malignancies. Front Matter....Pages i-x Overview: Rational Basis for Development of Fluoropyrimidine/5-Formyltetrahydrofolate Combination Chemotherapy....Pages 1-11 The Natural and Unnatural Diastereomers of Leucovorin: Aspects of their Cellular Pharmacology....Pages 13-24 Distribution and Metabolism of Calcium Leucovorin in Normal and Tumor Tissue....Pages 25-38 Role of Dosf, Schedule and Route of Administration of 5-Formyltetra-Hydrofolate: Preclinical and Clinical Investigations....Pages 39-52 Pharmacokinetic Analysis of (6S)-5-Formyltetrahydrofolate (1-CF), (6R)-5-Formyltetrahydrofolate (d-CF) and 5-Methyltetrahydrofolate (5-CH 3 -THF) in Patients Receiving Constant i.v. Infusion of High-Dose (6R,S)-5-Formyltetrahydrofolate (Leucovorin)....Pages 53-58 The Role of Thymidylate Synthase in the Response to Fluoropyrimidine-Folinic Acid Combinations....Pages 59-69 Tumor Cell Responses to Inhibition of Thymidylate Synthase....Pages 71-83 Selectivity of CF and 5-Fluorouracil: Critical Role of Polyglutamylation....Pages 85-95 Methods for Thymidylate Synthase Pharmacodynamics: Serial Biopsy, Free and Total TS, FdUMP and dUMP, and H 4 PteGlu and CH 2 -H 4 PteGlu Assays....Pages 97-106 The Treatment of Metastatic Breast Cancer with 5-Fluorouracil and Leucovorin....Pages 107-112 Thymidylate Synthase and Fluorouracil....Pages 113-125 Mechanisms for Cisplatin-FUra Synergism and Cisplatin Resistance in Human Ovarian Carcinoma Cells both in vitro and in vivo ....Pages 127-135 Summation of Session 1....Pages 137-137 Summation of Session II....Pages 139-141 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....Pages 143-155 Mount Sinai Clinical Experience with Leucovorin and 5-Fluorouracil....Pages 157-166 High-Dose Weekly Oral Leucovorin and 5-Fluorouracil in Previously Untreated Patients with Advanced Colorectal Carcinoma: A Phase I Study....Pages 167-172 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....Pages 173-184 5-Fluorouracil (FUra) and Folinic Acid (FA) Therapy in Patients with Colorectal Cancer....Pages 185-192 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....Pages 193-199 Clinical Experience with CF-FUra....Pages 201-211 A Randomized Trial of 5-Fluorouracil Alone Versus 5-Fluorouracil and High Dose Leucovorin in Untreated Advanced Colorectal Cancer Patients....Pages 213-218 Pharmacodynamics of 5-Fluorouracil and Leucovorin....Pages 219-224 5-Fluorouracil and 5-Formyltetrahydrofolate in Advanced Malignancies....Pages 225-232 Folinic Acid (CF)/5-Fluorouracil (FUra) Combinations in Advanced Gastrointestinal Carcinomas....Pages 233-243 Effective Salvage Therapy for Refractory Disseminated Breast Cancer with 5-Fluorouracil and High-Dose Continuous Infusion Folinic Acid....Pages 245-253 Progress Report on a Phase II Trial of 5-Fluorouracil Plus Citrovorum Factor in Women with Metastatic Breast Cancer....Pages 255-259 Adjuvant Therapy for Colorectal Cancer: The NSABP Clinical Trials....Pages 261-266 Chemotherapy of Advanced and Relapsed Squamous Cell Cancer of the Head and Neck with Split-Dose Cisplatinum (DDP), 5-Fluorouracil (Fura) and Leucovorin (CF)....Pages 267-273 5-Fluorouracil/Folinic Acid/Cisplatin-Combination and Simultaneous Accelerated Split-Course Radiotherapy in Advanced Head and Neck Cancer....Pages 275-284 Progress Report on Studies of FAM-CF for Gastric Cancer and Intraperitoneal Administration of FUra-CF Followed by Cisplatin (DDP)....Pages 285-293 Clinical Experience with 5-FU/DDP ± OHDW Combination Chemotherapy in Patients with Advanced Colorectal Carcinoma....Pages 295-302 5-Fluorouracil and Folinic Acid: Summary of Clinical Experience....Pages 303-311 Panel Discussion of Future Directions....Pages 313-327 Back Matter....Pages 329-336