Biomodulation of 5-fluorouracil with antifolates Journal Article
| Author: | Bertino, J. R. |
| Article Title: | Biomodulation of 5-fluorouracil with antifolates |
| Abstract: | The cytotoxic activity of 5-fluorouracil (5-FU) can be modulated by coadministration of antifolates or leucovorin (LV). Although a recent meta- analysis concluded that a sequential combination of methotrexate (MTX) and 5- FU was superior to 5-FU alone in terms of response rate and survival, combination MTX and 5-FU therapy has not been actively pursued by many leading cancer centers. We have subsequently investigated the combination of trimetrexate (TMTX) plus 5-FU/LV. Unlike MTX, TMTX does not compete with LV for up-take or polyglutamylation. In a phase I clinical study, combination TMTX/5-FU/LV was well tolerated and produced an overall response rate of 20% in previously treated colorectal cancer patients. In a follow-up phase II clinical study, this combination was highly active in patients with advanced colorectal cancer, demonstrating a 50% overall response rate. Currently, a phase III clinical trial is in progress comparing this regimen with combination 5-FU/LV. |
| Keywords: | clinical trial; review; fluorouracil; cancer combination chemotherapy; drug efficacy; drug potentiation; methotrexate; colorectal cancer; antimetabolites, antineoplastic; antineoplastic combined chemotherapy protocols; colorectal neoplasms; folinic acid; drug response; thymidine kinase; drug cytotoxicity; folic acid antagonist; thymidylate synthase; folic acid antagonists; leucovorin; orotate phosphoribosyltransferase; thymidine phosphorylase; uridine phosphorylase; clinical trials; trimetrexate; gastrointestinal carcinoma; methylenetetrahydrofolic acid; humans; human; priority journal; floxuridine phosphate |
| Journal Title: | Seminars in Oncology |
| Volume: | 24 |
| Issue: | 5 Suppl. 18 |
| ISSN: | 0093-7754 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1997-10-01 |
| Start Page: | S18-52 |
| End Page: | S18-56 |
| Language: | English |
| PUBMED: | 9420021 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 17 March 2017 -- Source: Scopus |
