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Annals of Oncology 13:92-94, 2002
© 2002 European Society for Medical Oncology

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

C. J. A. Punt1,+, C. D. Blanke2, J. Zhang3 and L. Hammershaimb3

1University Medical Centre, St Radboud, Nijmegen, The Netherlands; 2Oregon Health and Science University, Portland, OR; 3MedImmune Oncology, Inc., Gaithersburg, MD, USA

Received 7 September 2001; accepted 11 September 2001.

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.

Key words: biochemical modulation, colorectal cancer, 5-fluorouracil, leucovorin, randomised trial, trimetrexate


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