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)

• Published in: European journal of cancer (1990) Vol. 44; no. 15; pp. 2204 - 2211
• Main Authors: Popov, Ivan, Carrato, Alfredo, Sobrero, Alberto, Vincent, Mark, Kerr, David, Labianca, Roberto, Raffaele Bianco, Angelo, El-Serafi, Mostafa, Bedenne, Laurent, Paillot, Bernard, Mini, Enrico, Sanches, Evaristo, Welch, John, Collette, Laurence, Praet, Michel, Wils, Jacques
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2008; Elsevier
• Subjects: Adjuvant treatment; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy, Adjuvant; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Colonic Neoplasms - surgery; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Hematology, Oncology and Palliative Medicine; Humans; Leucovorin - administration & dosage; Leucovorin - adverse effects; Male; Medical sciences; Middle Aged; PETACC-1; Pharmacology. Drug treatments; Quinazolines - adverse effects; Quinazolines - therapeutic use; Raltitrexed; Randomised clinical trial; Survival Analysis; Thiophenes - adverse effects; Thiophenes - therapeutic use; Treatment Outcome; Tumors; Young Adult; Europe; Raltitrexed; PETACC-1; Colon cancer; Randomised clinical trial; Adjuvant treatment; Antineoplastic agent; Phase III trial; Quinazoline derivatives; Calcium folinate; Cancerology; Intestinal disease; Clinical trial; Fluorouracil; Enzyme; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; Standards; Colonic disease; Chemotherapy; Treatment; Bolus injection; Antimetabolic; Methyltransferases; Pyrimidine derivatives; Digestive diseases; Comparative study; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2008.07.002

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 α = 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.