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Semimonthly Versus Monthly Regimen of Fluorouracil and Leucovorin Administered for 24 or 36 Weeks as Adjuvant Therapy in Stage II and III Colon Cancer: Results of a Randomized Trial

Thierry André, Philippe Colin, Christophe Louvet, Erik Gamelin, Olivier Bouche, Emmanuel Achille, Nicolas Colbert, Catherine Boaziz, Pascal Piedbois, Nicole Tubiana-Mathieu, Arnaud Boutan-Laroze, Michel Flesch, Marc Buyse, Aimery de Gramont

From the Hôpital Tenon, Hôpital Saint-Antoine, Hôpital St Joseph, and Groupe d’Etude et de Recherche Clinique en Oncologie Radiotherapie, Paris; Clinique Courlancy, and Centre Hospitalier Universitaire de Reims, Reims; Centre Paul Papin, Angers; Clinique de l’Orangerie, Strasbourg; Centre Paris Nord, Sarcelles; Hôpital Henri Mondor, Creteil; Centre Hospitalier Universitaire de Limoges, Limoges; Centre Hospitalier d’Argenteuil, Argenteuil; Hôpital Devron, Dijon, France; and International Drug Development Institute, Brussels, Belgium.

Address reprint requests to Thierry André, Service d’Oncologie Médicale, Hôpital Tenon, 4 rue de la Chine, F-75970 Paris Cedex 20, France; email: thierry.andre{at}tnn.ap-hop-paris.fr.

Purpose: This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes’ B2) and III (Dukes’ C) colon cancer.

Patients and Methods: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m², respectively) as a 2-hour infusion, followed by a 400 mg/m² FU bolus and 600 mg/m² of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m² of FU as a 15-minute infusion.

Results: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P = .74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P = .63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P = .18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P < .001).

Conclusion: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.

Supported by grants from Association Pour la Recherche en Cancérologie, Hôpital Tenon, Paris, France, and from Wyeth Lederle, Puteaux, Baxter, Maurepas, and Roche Laboratories, Neuilly sur Seine, France.

Presented in part at the Thirty-Eighth Annual Meeting of the American Society of Clinical Oncology, May 18–21, 2002, Orlando, FL.

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