A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer Journal Article
| Authors: | Blanke, C. D.; Shultz, J.; Cox, J.; Modiano, M.; Isaacs, R.; Kasimis, B.; Schilsky, R.; Fleagle, J.; Moore, M.; Kemeny, N.; Carlin, D.; Hammershaimb, L.; Haller, D. |
| Article Title: | A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer |
| Abstract: | Background: Trimetrexate (TMTX) biochemically modulates 5-fluorouracil (5-FU) and leucovorin (LCV). Two phase II trials demonstrated promising activity for TMTX/5-FU/LCV in patients with untreated advanced colorectal cancer (ACC). This trial was designed to demonstrate the safety and efficacy of TMTX/5-FU/LCV as first-line treatment in ACC. Patients and methods: Eligible patients with ACC were randomized in double-blind fashion to receive placebo or TMTX (110 mg/m2) intravenously (i.v.) followed 24 h later by i.v. LCV 200 mg/m2, and 5-FU 500 mg/m2 plus oral LCV rescue. Both schedules were given weekly for 6 weeks every 8 weeks. Patients were evaluated for progression-free survival (PFS), overall survival (OS), tumor response, quality of life (QoL) and toxicity. Results: A total of 382 eligible patients were randomized. Significant toxicities were noted more frequently with TMTX/5-FU/LCV. Diarrhea was the most common grade 3 or 4 side-effect (41% and 28% on the TMTX and placebo arms, respectively). QoL scores and response rates did not differ between treatment arms. PFS was 5.3 months and 4.4 months in the TMTX and placebo arms, respectively (P = 0.77); Wilcoxon). OS was 15.8 months and 16.8 months, respectively (P = 0.73; Wilcoxon). Conclusions: The addition of TMTX to a weekly regimen of 5-FU/LCV worsened grade 3 or 4 diarrhea. The inclusion of TMTX did not yield any significant improvements in response rate, PFS or OS. |
| Keywords: | adolescent; adult; cancer survival; controlled study; aged; aged, 80 and over; middle aged; survival rate; major clinical study; clinical trial; fatigue; neutropenia; fluorouracil; advanced cancer; cancer growth; diarrhea; drug efficacy; drug safety; colorectal cancer; quality of life; controlled clinical trial; nausea; randomized controlled trial; vomiting; antineoplastic combined chemotherapy protocols; time factors; abdominal pain; colorectal neoplasms; statistical analysis; disease progression; folinic acid; drug response; loperamide; phase 3 clinical trial; double blind procedure; double-blind method; 5-fluorouracil; randomized trial; leucovorin; hypersensitivity reaction; trimetrexate; biochemical modulation; humans; human; male; female; priority journal; article |
| Journal Title: | Annals of Oncology |
| Volume: | 13 |
| Issue: | 1 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2002-01-01 |
| Start Page: | 87 |
| End Page: | 91 |
| Language: | English |
| DOI: | 10.1093/annonc/mdf043 |
| PUBMED: | 11863117 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
