Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1).

Abstract

OBJECTIVES:

PETACC-1 assessed if raltitrexed is non-inferior to 5-fluorouracil and leucovorin for relapse-free survival (RFS) and overall survival (OS) in adjuvant stage III colon cancer.

METHODS:

Non-inferiority required both HR for RFS and OS<1.25 at 1-sided alpha=0.05. Patients (1921) were randomised to six cycles of 5-FU/LV (n=969) or eight cycles of raltitrexed (n=952). We report the final results in 993 eligible patients who started and completed the allocated treatment (489 5-FU/LV and n=504 Raltitrexed) of whom respectively 146 and 148 died, respectively.

RESULTS:

The trial closed prematurely when 17 (1.9%) raltitrexed-related deaths were reported. Haematological and gastrointestinal toxicities were more frequent with 5-FU/LV, liver toxicities with raltitrexed. Raltitrexed was stopped for toxicity in 13.2% and 5-FU/LV in 8.5%. Sixty-day mortality was 9% versus 7%. With 4.1 years median follow-up, the HR for RFS was 1.16 (90% CI 0.99-1.37) and that for OS was 1.01 (90% CI 0.84-1.23).

CONCLUSION:

The trial failed to demonstrate non-inferiority of raltitrexed.

FUNDING:

Free drugs and financial support from AstraZeneca.

• Authors: Ivan Popov, Alfredo Carrato, Alberto Sobrero, Mark Vincent, David Kerr, Roberto Labianca, Angelo Raffaele Bianco, Mostafa El-Serafi, Laurent Bedenne, Bernard Paillot, Enrico Mini, Evaristo Sanches, John Welch, Laurence Collette, Michel Praet, Jacques Wils
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 44 Issue 15 Pg. 2204-11 (Oct 2008) ISSN: 1879-0852 [Electronic] England
• PMID: 18707870 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Quinazolines
• Thiophenes
• raltitrexed
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Chemotherapy, Adjuvant
• Colonic Neoplasms (drug therapy, pathology, surgery)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Quinazolines (adverse effects, therapeutic use)
• Survival Analysis
• Thiophenes (adverse effects, therapeutic use)
• Treatment Outcome
• Young Adult