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Oral fluoropyrimidines versus 5-fluorouracil for colorectal cancer: Results of a systematic review and meta-analysis.

4111 Background: Previous studies showed that continuous intravenous infusion (cIV) of 5-fluorouracil (5FU) is associated with best tumor response in comparison to bolus 5-FU and perhaps, a slight increase of overall survival. There are some non-inferiority trials comparing oral fluoropyrimidines with bolus or cIV of 5FU, but there is still no definitive evidence of equivalence. This systematic review evaluated the efficacy of oral fluoropyrimidines compared to bolus or cIV administration of 5FU in colorectal cancer.


METHODS
PubMed, EMBASE, CENTRAL and LILACS databases were searched. Eligible studies were randomized trials (RCTs) comparing chemotherapy regimens containing oral fluoropyrimidines (capecitabine, UFT or Tegafur) and 5FU (bolus or cIV) in patients with colorectal cancer. The primary outcome was overall survival (OS). Secondary outcomes included response rate (RR), progression-free survival (PFS) and disease-free-survival (DFS). Hazard Ratio (HR) and Odds Ratio (OR) with fixed effect model were used for meta- analysis and were expressed with 95% confidence intervals (CI).


RESULTS
We included results from 20 RCTs, with a total of 14,779 patients. Compared to cIV of 5FU, capecitabine resulted in lower RR (OR 0.82; 95% CI 0.72 to 0.95; p=0.006), shorter PFS (HR 1.09; 95% CI 1.01 to 1.17; p=0.02) and was associated with a non- significant reduction in OS (HR 1.05; 95%CI 0.97 to 1.14; p=0.23). Compared to bolus 5FU, capecitabine resulted in lower RR (OR 0.80; 95% CI 0.65 to 0.98; p=0.004), but similar OS and PFS. Compared to bolus 5FU, the use of other fluoropyrimidines resulted in similar RR, OS and PFS.


CONCLUSIONS
Oral fluoropyrimidines are equivalent to bolus 5FU in terms of efficacy, but provides less benefit than cIV 5FU. Combination chemotherapy with cIV 5FU remains the first choice for patients with colorectal cancer. [Table: see text].