Integrated analysis of overall survival in two randomised studies comparing 5-fluorouracil/leucovorin with or without trimetrexate in advanced colorectal cancer

C. J A Punt, Charles Blanke, J. Zhang, L. Hammershaimb

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Abstract

Background: Two randomised studies were performed with trimetrexate (TMTX) as a biochemical modulator of 5-fluorouracil (5-FU)/leucovorin (LV) in advanced colorectal cancer (ACC), one in Europe and one in the United States. Both studies were similarly designed to detect a statistically significant difference in progression-free survival (PFS). Overall survival (OS), however, was later adopted as the primary outcome measure for approvability of agents for first-line treatment of ACC. Therefore, an integrated analysis of survival data from the European and USA trials was performed to detect a clinically relevant difference in survival. Patients and methods: The experimental arm was identical in both studies and consisted of TMTX 110 mg/m2 intravenously (i.v.) followed 24 h later by i.v. LV 200 mg/m2/5-FU 500 mg/m2 plus oral LV rescue. The 5-FU dose in the control arm was 600 mg/m2 in the European study and 500 mg/m2 in the USA study, and the USA study was placebo-controlled. Treatment was given weekly for 6 weeks every 8 weeks. Results: A total of 746 patients were analysed. Median OS was 13.0 months for 5-FU/LV and 14.6 months for TMTX/5-FU/LV (P = 0.15; Wilcoxon). Median PFS was 4.4 months and 5.4 months, respectively (P = 0.07; Wilcoxon). Conclusions: The addition of TMTX to a weekly regimen of 5-FU/LV does not improve the outcome for patients with ACC.

Original languageEnglish (US)
Pages (from-to)92-94
Number of pages3
JournalAnnals of Oncology
Volume13
Issue number1
DOIs
StatePublished - 2002

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Trimetrexate
Leucovorin
Survival Analysis
Fluorouracil
Colorectal Neoplasms
Disease-Free Survival
Survival
Placebos
Outcome Assessment (Health Care)
Therapeutics

Keywords

  • 5-fluorouracil
  • Biochemical modulation
  • Colorectal cancer
  • Leucovorin
  • Randomised trial
  • Trimetrexate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Integrated analysis of overall survival in two randomised studies comparing 5-fluorouracil/leucovorin with or without trimetrexate in advanced colorectal cancer. / Punt, C. J A; Blanke, Charles; Zhang, J.; Hammershaimb, L.

In: Annals of Oncology, Vol. 13, No. 1, 2002, p. 92-94.

Research output: Contribution to journalArticle

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AB - Background: Two randomised studies were performed with trimetrexate (TMTX) as a biochemical modulator of 5-fluorouracil (5-FU)/leucovorin (LV) in advanced colorectal cancer (ACC), one in Europe and one in the United States. Both studies were similarly designed to detect a statistically significant difference in progression-free survival (PFS). Overall survival (OS), however, was later adopted as the primary outcome measure for approvability of agents for first-line treatment of ACC. Therefore, an integrated analysis of survival data from the European and USA trials was performed to detect a clinically relevant difference in survival. Patients and methods: The experimental arm was identical in both studies and consisted of TMTX 110 mg/m2 intravenously (i.v.) followed 24 h later by i.v. LV 200 mg/m2/5-FU 500 mg/m2 plus oral LV rescue. The 5-FU dose in the control arm was 600 mg/m2 in the European study and 500 mg/m2 in the USA study, and the USA study was placebo-controlled. Treatment was given weekly for 6 weeks every 8 weeks. Results: A total of 746 patients were analysed. Median OS was 13.0 months for 5-FU/LV and 14.6 months for TMTX/5-FU/LV (P = 0.15; Wilcoxon). Median PFS was 4.4 months and 5.4 months, respectively (P = 0.07; Wilcoxon). Conclusions: The addition of TMTX to a weekly regimen of 5-FU/LV does not improve the outcome for patients with ACC.

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