[Frontiers in Bioscience E3, 1475-1482, June 1, 2011]

[Frontiers in Bioscience E3, 1475-1482, June 1, 2011]

Additional 5-FU-LV significantly increases survival in gastrointestinal cancer

Andrea Nicolini¹, Massimo Conte², Giuseppe Rossi³, Paola Ferrari¹, Michael Duffy⁴, Vivian Barak⁵, Angelo Carpi⁶, Paolo Miccoli²

1Department of Internal Medicine, ²Department of Surgery, University of Pisa, ³Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, CNR, Pisa, Italy, ⁴Department of Pathology and Laboratory Medicine, St Vincent's University Hospital, Dublin and Conway Institute, UCD School of Medicine and Medical Science, University College, Dublin, Ireland, ⁵Hadassah-Hebrew University Medical Center, Jerusalem, Israel, ⁶Department of Reproduction and Ageing, University of Pisa; Italy. ^{1, 4, 5}Focus Groups, European Group on Tumor Markers (EGTM)

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods: 3.1. Patients; 3.2. Clinical and pathological features; 3.3. Study design; 3.4. Adjuvant chemotherapy (CT) after curative resection; 3.5. Additive post-adjuvant 5-FU-LV cycles in the study group; 3.6. Intensive post-operative monitoring; 3.7. Statistical analysis
4. Results: 4.1. Follow-up; 4.2. Five-year OS and DFS
5. Discussion: 5.1. Improved outcome and shortcomings; 5.2. The study reasons and interpretation
6. References

1. ABSTRACT

Metastatic colorectal and other locally advanced gastrointestinal (G.I.) cancers often recur after curative resection. Many mechanisms of tumor growth and/or immune escape by residual cancer cells may provoke tumor progression. Long-term, cytostatic action with repeated post-adjuvant administration of 5-fluorouracil (FU)-leucovorin (LV) cycles may interrupt or downregulate these mechanisms and favor the recovery and/or increase the immune system activity. Seventy patients were considered. An active prospective cohort including 21 patients (study group) was matched in a 1:1 ratio with a retrospective parallel control group of 21 patients. The study group received long-term repeated post-adjuvant administration of 5-FU-LV cycles, while the matched control group was conventionally treated. Statistical analysis was performed by Kaplan-Meier method and Cox's proportional hazard regression model. The five-year disease-free survival (DFS) was 77.0 + 10.1% and 31.7 + 10.6% (p = 0.001; hazard ratio (HR) 5.3, 95% C.I.: 1.7-16.1, p = 0.003), while the five-year overall survival (OS) was 88.0 + 8.1% and 37.0 + 10.7% (p = 0.001; HR 8.9, 95% C.I.: 2.0-39.9, p = 0.004) in the study group and in matched controls respectively. These findings suggest a relevant improvement in the outcome of this population by an intermittent and prolonged cytostatic effect with 5-FU-LV.