Introduction Colorectal carcinoma is the most common gastrointestinal malig- nancy worldwide, with nearly 1 million newly diagnosed cases and 500,000 people dying of the disease each year. More than 40% of pa- tients who undergo potentially curative surgery alone will ultimately relapse. 1 The purpose of adjuvant chemotherapy is to reduce the risk of recurrence of the cancer either locally or at distant metastatic sites. 5-Fluorouracil (5-FU) modulated by leucovorin (LV) was the rec- ommended adjuvant chemotherapy for patients with stage III colon cancer until 2004, when the MOSAIC (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treat- ment of Colon Cancer) trial showed a superiority of adding oxaliplatin to this combination (FOLFOX4). 1 The mechanisms of action of 5-FU at the cellular level are mul- tifactorial and include (1) transport, metabolism, and incorporation into cellular RNA 2,3 ; (2) incorporation into cellular DNA 4 ; (3) potent inhibition of the target enzyme thymidylate synthase (TS) by the ac- tive metabolite of 5-FU (2'-deoxy-5'-fluorouridine-5'-monophosphate; FdUMP) 5 ; (4) catalysis by TS of the conversion of dUMP to thymi- dylic acid monophosphate, for which 5, 10-methylenetetrahydrofolate (MTHF) is the methyl donor. Inhibition of TS by FdUMP is mediated by the formation of a covalent complex between FdUMP, TS, and Clinical Colorectal Cancer April 2010 | E5 Abstract Comparison of the Levogyre and Dextro-Levogyre Forms of Leucovorin in a Phase III Trial of Bimonthly LV5FU2 Versus Monthly 5-Fluorouracil and High-Dose Leucovorin for Patients With Stage II and III Colon Cancer (GERCOR C96.1) Isabelle Baumgaertner, 1 Emmanuel Quinaux, 2 Ahmed Khalil, 3 Christophe Louvet, 4 Marc Buyse, 2 Aimery de Gramont, 4 Thierry André, 1 for the GERCOR Group Background: These analyses compare the safety and efficacy of 2 forms (levogyre [L] and dextro-levogyre [DL]) of leucovorin (LV) when used with 5-fluorouracil (5-FU) for the adjuvant treatment of patients with stage II and III colon cancer. Materials and Methods: The analysis used primary efficacy and safety data of a phase III trial comparing monthly 5-FU/LV or bimonthly LV5FU2 (LV 200 mg/m 2 intravenously over 2 hours followed by 5-FU 400 mg/m 2 bolus and then 600 mg/m 2 continuous intravenous infusion over 22 hours, days 1 and 2, every 2 weeks). In both regimens, depending on the choice made by each center, patients received either DL-LV (200 mg/m 2 ) or L-LV (100 mg/m 2 ). Results: L-LV and DL-LV were administered respectively to 60% (n = 519) and 40% (n = 357) of the patients. Important prognostic characteristics were well balanced between the 2 groups. The proportion of any grade 3/4 toxicity was 20% in the L-LV group and 17% in the DL-LV group. There was no statistical difference in terms of toxicity between the 2 groups. The median follow-up time was 6.1 years. There were no statistically significant differences between L-LV and DL-LV in terms of either disease-free survival (66.7% vs. 67.2%; hazard ratio [HR], 1.03; 95% CI, 0.82-1.31; P = .78) or overall survival (78.2% vs. 74.5%; HR, 1.28; 95% CI, 0.97-1.69; P = .078). Conclusion: This study supports the use of either DL (200 mg/m 2 ) or L (100 mg/m 2 ) LV in association with 5-FU as adjuvant treatment of patients with colon cancer. Clinical Colorectal Cancer, Vol. 9, No. 2, E5-E10, 2010; DOI: 10.3816/CCC.2010.n.027 Keywords: Adjuvant treatment, de Gramont regimen, Pharmacokinetics, Stereoisomers Review This summary may include the discussion of investigational and/or unlabeled uses of drugs and/or devices that may not be approved by the FDA. Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1533-0028, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. www.copyright.com 978-750-8400. 1 Department of Hepatogastroenterology, Hôpital Pitié-Salpétrière, Paris, France 2 International Drug Development Institute, Louvain-la-Neuve, Belgium 3 Department of Medical Oncology, Hôpital Tenon, Paris, France 4 Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France Submitted: Nov 2, 2009; Accepted: Oct 29, 2009 Address for correspondence: Thierry André, MD, Department of Hepatogastroenterology, Hôpital Pitié-Salpétrière, Paris 75013, France Fax: 01-42-16-14-25; e-mail: thierry.andre@psl.aphp.fr