Trial of sequential trimetrexate, fluorouracil, and high-dose leucovorin in previously treated patients with gastrointestinal carcinoma Journal Article
| Authors: | Conti, J. A.; Kemeny, N.; Seiter, K.; Goker, E.; Tong, W.; André, M.; Ragusa, K.; Bertino, J. R. |
| Article Title: | Trial of sequential trimetrexate, fluorouracil, and high-dose leucovorin in previously treated patients with gastrointestinal carcinoma |
| Abstract: | Purpose: Trimetrexate (TMTX) is a dihydrofolate reductase inhibitor, which, like methotrexate (MTX), has been shown to potentiate fluorouracil (FU) cytotoxicity by increasing phosphoribosylpyrophosphate (PRPP) levels. We investigated the safety and efficacy of a sequential TMTX/FU/leucovorin (LV) combination. Patients and Methods: Forty-one patients with advanced gastrointestinal carcinoma (mostly colorectal) received variable doses of TMTX followed 24 hours later by FU/LV (500 mg/m2 of each drug). Almost all patients had received previous chemotherapy. The initial 19 patients were treated on a 3-week-on/1-week-off schedule without any significant toxicity; the remaining patients were treated for 6 consecutive weeks followed by a 2- week rest period. TMTX was escalated in 30-mg/m2 increments from 20 to 110 mg/m2 in separate patient cohorts. When the 110-mg/m2 dose of TMTX was reached, the FU dose was escalated from 500 mg/m2 to 600 mg/m2. Results: The partial response (PR) rate in assessable patients with colorectal cancer (all previously treated) was 20% (seven of 35; 95% confidence interval, 7% to 33%), and with other gastrointestinal cancers was one of four patients. Median survival has not been reached with a median follow-up of 13.5 months. The maximum-tolerated dose (MTD) was 110 mg/m2 for TMTX, 500 mg/m2 for FU, and 500 mg/m2 for LV on a 6-weeks-on/2-weeks-off cycle. The principal toxicities were grade 3 or 4 diarrhea, which occurred in 17% of patients, and hypersensitivity reactions, which occurred in 26% of patients. Conclusion: TMTX can be administered at maximal doses in combination with FU and LV without increasing toxicity. The PR rate of 20% in advanced colorectal carcinoma patients previously treated with chemotherapy is encouraging and merits further study. |
| Keywords: | adult; cancer survival; clinical article; aged; clinical trial; fluorouracil; advanced cancer; cancer combination chemotherapy; diarrhea; gastrointestinal hemorrhage; follow up; colorectal carcinoma; drug hypersensitivity; folinic acid; pancreatitis; drug response; pancytopenia; hemorrhagic gastritis; intravenous drug administration; trimetrexate; gastrointestinal carcinoma; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 12 |
| Issue: | 4 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 1994-04-01 |
| Start Page: | 695 |
| End Page: | 700 |
| Language: | English |
| DOI: | 10.1200/jco.1994.12.4.695 |
| PROVIDER: | scopus |
| PUBMED: | 7512128 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work