J Cancer 2011; 2:177-185. doi:10.7150/jca.2.177

Research Paper

Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study

Arie Figer1 *, Aviram Nissan2 * ✉, Adi Shani3, Riva Borovick4, Mariana Stiener4, Mario Baras5, Herbert R. Freund2, Aaron Sulkes6, Alexander Stojadinovic7, Tamar Peretz8

1. Department of Oncology, Tel Aviv-Souraski Medical Center, Tel Aviv, Israel.
2. The Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
3. Department of Oncology, Kaplan Medical Center, Rehovot, Israel.
4. Lin Oncology Center, Haifa, Israel.
5. The Department of Biostatistics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
6. Department of Oncology, Rabin Medical Center, Petah Tikva, Israel.
7. Department of Surgery, Walter Reed Army Medical Center, and the United States Military Cancer Institute, Washington, D.C., USA.
8. The Department of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
* Share first authorship.

Abstract

Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV).

Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months.

Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02) and gastrointestinal toxicity with 5FU+LV (p=0.03). Female patients treated with 5FU+LEV had improved overall survival.

Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

Keywords: colorectal cancer, adjuvant chemotherapy, 5-fluorouracil, leucovorin, levamisole, survival

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How to cite this article:
Figer A, Nissan A, Shani A, Borovick R, Stiener M, Baras M, Freund HR, Sulkes A, Stojadinovic A, Peretz T. Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study. J Cancer 2011; 2:177-185. doi:10.7150/jca.2.177. Available from http://www.jcancer.org/v02p0177.htm