The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy

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