Background The objective of this study is to conduct a pooled

Background The objective of this study is to conduct a pooled analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials involving surgery and surgery plus AV-412 5-fluorouracil and leucovorin (5-FU/LV) to compare survival and establish a baseline from which to evaluate future studies. Time-to-event by treatment group was examined using adjusted Kaplan-Meier estimates and multivariable Cox regression analysis. Results There were 2 966 eligible patients: 693 (23%) surgery and 2 273 (77%) surgery plus 5-FU/LV; AV-412 1 255 (42%) stage II and 1 711 (58%) stage III. Age ≥ 60 years {hazard ratio (HR)=1.36 P<0.000] male AV-412 gender (HR=1.20 P=0.0012) and more AV-412 nodes positive or fewer nodes examined (P< 0.0001) were associated with worse survival. At 5 years the adjusted OS was 0.62 [confidence interval (CI)= 0.60-0.63] in the surgery group and 0.76 (CI= 0.74- 0.78) in the surgery plus 5-FU/LV group. Treatment with 5-FU/LV was associated with improved outcome compared with surgery: OS (HR=0.62 P<0.0001) DFS (HR=0.66 P<0.0001) and RFI (HR=0.64 P<0.0001). Improved OS with adjuvant treatment was seen in both stage II (HR=0.58 95 CI=0.48-0.71) and stage III disease (HR=0.65 95 CI=0.55-0.75). Conclusions This analysis demonstrates that treatment of colon cancer patients with 5-FU/LV following surgery provides benefit over surgery alone and can provide anticipated survival outcomes from which to compare modern adjuvant trials. in a recent pooled analysis of the Adjuvant Colon Cancer Endpoint Rabbit Polyclonal to RAB5C. (ACCENT) Group. In light of more effective systemic control what will be the role and timing of surgical and systemic therapy for recurrent disease? Will recurrences be noted after the 5-year mark if modern adjuvant therapy proves more effective? Follow up recommendations need to be re-examined. Current chemotherapy provides a meaningful survival advantage to patients with stage IV colon cancer. Unfortunately these agents have not altered the ultimate outcome in stage IV disease. Eradication through surgical resection or ablation of microscopic residual disease is still required.24 This stands in direct contrast to the results presented here: 5-FU/LV is associated with a measurable survival advantage (approximately 15% for stage III) lasting 10 to 15 years AV-412 following surgery. This may represent effective treatment of “unestablished” micrometastatic disease rather than early treatment of unrecognized stage IV disease. In conclusion this analysis provides the observed survival outcome for resected colon cancer patients examining primary treatment modalities utilized in the 1970s through the 1990s. Two messages should be learned from these results. First all gross disease and all regional lymph nodes at risk for metastatic disease must be surgically resected because surgery alone can cure the majority of stage II and III colon cancer patients. The incremental benefits of adjuvant therapy are unlikely ever to match these surgical results. Second we should continue to study the long-term effects of adjuvant therapy in both stage II and III disease. Important questions remain. How do the results of 5-FU/LV therapy compare with the modern agents being examined today? For the assumed incremental benefit what will be the added costs and toxicities? Identification of the highest-risk subset for adjuvant therapy still needs to be improved. These results can be used to provide comparison survival outcomes from which to compare modern adjuvant trials. Our future tasks must be to maximize the utilization of both surgical and adjuvant therapy while designing new clinical trials to improve on these results. Acknowledgments These studies were supported by: Public Health Service grants U10-CA-12027 U10-CA-69651 U10-CA-37377 and U10-CA-69974 from the National Cancer Institute Department of Health and Human Services. Footnotes Clinical Trial Registration: NSABP C-01: “type”:”clinical-trial” attrs :”text”:”NCT00427570″ term_id :”NCT00427570″NCT00427570; NSABP C-02: “type”:”clinical-trial” attrs :”text”:”NCT00427310″ term_id :”NCT00427310″NCT00427310; NSABP C-03: PDQ: NSABP C-03; NSABP C-04: “type”:”clinical-trial” attrs :”text”:”NCT00425152″ term_id :”NCT00425152″NCT00425152; NSABP C-05: PDQ: NSABP C-05 REFERENCES 1 Jemal A Siegel R Ward E et al. Cancer Statistics 2008 CA Cancer J Clin. 2008;58:71–96. Epub 2008 Feb 20. [PubMed] 2 Moertel CG Fleming TR Macdonald JS et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage.