Journal of Clinical Oncology, Vol 14, 2274-2279, Copyright © 1996 by American Society of Clinical Oncology

ARTICLES

Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial.Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1

E Jager, M Heike, H Bernhard, O Klein, G Bernhard, D Lautz, J Michaelis, KH Meyer zum Buschenfelde and A Knuth
II. Medizinische Klinik, Hamatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.

PURPOSE: To determine the most effective dose of leucovorin (folinic acid [FA]) within a weekly bolus fluorouracil (FU) schedule, we conducted a randomized multicenter trial to compare therapeutic effects and toxicity of high-dose FA versus low-dose FA combined with FU at equal doses in both treatment groups. PATIENTS AND METHODS: Patients with measurable inoperable or metastatic colorectal cancer were randomized to receive weekly FU 500 mg/m2 by intravenous (IV) bolus combined with high-dose FA 500 mg/m2 (group A) or low-dose FA 20 mg/m2 (group B) by 2-hour infusion. RESULTS: Of 291 assessable patients (group A, n = 148; group B, n = 143), we observed, in group A, complete response (CR)/partial response (PR) in 32 (21.6%), no change (NC) in 64 (43.2%), and progressive disease (PD) in 52 (35.1%); and in group B, CR/PR in 25 (17.5%), NC in 63 (44.1%), and PD in 55 (38.5%). The median response duration was 24.8 weeks in group A and 23.1 weeks in group B. Median progression-free intervals were 29.3 weeks (group A) and 30 weeks (group B). The median survival time was 55.1 weeks in group A and 54.1 weeks in group B. Overall toxicity was moderate. Mild nausea and vomiting, and stomatitis were common side effects in both groups. The incidence of World Health Organization (WHO) grade III/IV diarrhea was significantly higher in group A (40 v 23 patients). Severe side effects were observed only in a minority of patients in both arms. WHO grade IV diarrhea was observed in seven patients: four in group A and three in group B. The rate of toxicity-related adjustments of dose and schedule was comparable in both groups. CONCLUSION: High-dose FA/FU is not superior to low-dose FA/FU within a weekly treatment schedule. Response rates and survival were comparable in both treatment arms. Treatment- related toxicity was higher in group A (high-dose FA). Therefore, low- dose FA combined with weekly FU may be considered the preferred treatment for metastatic colorectal cancer.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. F. Engstrom, J. P. Arnoletti, A. B. Benson III, Y.-J. Chen, M. A. Choti, H. S. Cooper, A. Covey, R. A. Dilawari, D. S. Early, P. C. Enzinger, et al. Colon Cancer J Natl Compr Canc Netw, September 1, 2009; 7(8): 778 - 831. [Abstract] [PDF]

				H. J. Lim, S. Gill, C. Speers, B. Melosky, J. Barnett, C. Fitzgerald, S. O'Reilly, and H. Kennecke Impact of Irinotecan and Oxaliplatin on Overall Survival in Patients With Metastatic Colorectal Cancer: A Population-Based Study J. Oncol. Pract, July 1, 2009; 5(4): 153 - 158. [Abstract] [Full Text] [PDF]

				M. Schlemmer, M. Kuehl, A. Schalhorn, J. Rauch, K.-W. Jauch, and M. Hentrich Tissue Levels of Reduced Folates in Patients with Colorectal Carcinoma After Infusion of Folinic Acid at Various Dose Levels Clin. Cancer Res., December 1, 2008; 14(23): 7930 - 7934. [Abstract] [Full Text] [PDF]

				K. M. Field, S. Kosmider, M. Jefford, R. Jennens, M. Green, and P. Gibbs Chemotherapy Treatments for Metastatic Colorectal Cancer: Is Evidence-Based Medicine in Practice? J. Oncol. Pract, November 1, 2008; 4(6): 271 - 276. [Abstract] [Full Text] [PDF]

				P. A. Tang, S. M. Bentzen, E. X. Chen, and L. L. Siu Surrogate End Points for Median Overall Survival in Metastatic Colorectal Cancer: Literature-Based Analysis From 39 Randomized Controlled Trials of First-Line Chemotherapy J. Clin. Oncol., October 10, 2007; 25(29): 4562 - 4568. [Abstract] [Full Text] [PDF]

				S.-G. Kim, S. Y. Oh, H.-C. Kwon, S. Lee, J. H. Kim, S.-H. Kim, and H.-J. Kim A Phase II Study of Irinotecan with Bi-weekly, Low-dose Leucovorin and Bolus and Continuous Infusion 5-fluorouracil (Modified FOLFIRI) as Salvage Therapy for Patients with Advanced or Metastatic Gastric Cancer Jpn. J. Clin. Oncol., October 8, 2007; (2007) hym103v1. [Abstract] [Full Text] [PDF]

				J.-H. Lee, J.-H. Park, Y. Jung, J.-H. Kim, H.-S. Jong, T.-Y. Kim, and Y.-J. Bang Histone deacetylase inhibitor enhances 5-fluorouracil cytotoxicity by down-regulating thymidylate synthase in human cancer cells Mol. Cancer Ther., December 1, 2006; 5(12): 3085 - 3095. [Abstract] [Full Text] [PDF]

				L. B. Saltz Another Study of How to Give Fluorouracil? J. Clin. Oncol., October 15, 2003; 21(20): 3711 - 3712. [Full Text] [PDF]

				U. Vanhoefer, A. Harstrick, C.-H. Kohne, W. Achterrath, Y. M. Rustum, S. Seeber, and H. Wilke Phase I Study of a Weekly Schedule of Irinotecan, High-Dose Leucovorin, and Infusional Fluorouracil as First-Line Chemotherapy in Patients With Advanced Colorectal Cancer J. Clin. Oncol., March 1, 1999; 17(3): 907 - 907. [Abstract] [Full Text] [PDF]