Grothe, Wilfried

4555 Background: Combination chemotherapy is widely accepted for patients with advanced gastric cancer, but uncertainty remains regarding the choice of the regimen. Methods: Our objectives were to assess the effect of: 1) 5-FU/cisplatin combinations with versus without anthracyclines; 2) 5-FU/anthracycline combinations with versus without cisplatin; 3) Irinotecan versus non-irinotecan containing combination chemotherapies; 4) Docetaxel versus non-docetaxel containing combinations; on overall survival and toxicity. Search strategy: We searched: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, proceedings from DDW, ECCO, ESMO, ASCO until october 2006. Selection criteria: Randomised controlled trials on different combination chemotherapies as above in advanced gastric cancer. Results: 13 trials including in total 2,184 patients (pts) are included in this meta-analysis. Comparison 1) including 501 pts (HR 0.77; 95% CI 0.62–0.95); and 2) including 1,147 pts (HR 0.83; 95%CI 0.76–0.91) both demonstrate a significant survival benefit for three-drug regimens including 5-FU, anthracyclines and cisplatin. Among these, the rate of treatment-related deaths was higher when 5-FU was administered as bolus compared to infusional 5-FU (exact Mantel-Haenszel OR 2.33, p=0.285). Comparison 3) including 536 pts results in a HR of 0.88; 95% CI 0.73- 1.06. The rate of treatment related deaths was 0.7% versus 2.6% in the irinotecan versus non-irinotecan-containing arms (exact Mantel-Haenszel OR 0.275, p=0.166). Comparison 4) 4 relevant trials were identified. A meta-analysis will be performed as soon as the final results of at least 3 trials are available. Conclusions: Three-drug regimens containing 5-FU, anthracyclines and cisplatin achieve superior survival results compared to cisplatin/5-FU or antracycline/5-FU combinations. Among these, ECF (epirubicin, cisplatin and 5-FU) is tolerated best. Combinations including irinotecan demonstrate a non-significant trend towards better survival in this meta-analysis, but have never been compared against three-drug regimens containing 5-FU/cisplatin and an anthracycline. Supported by: KKS Halle, grant number [BMBF/FKZ 01GH01GH0105]. No significant financial relationships to disclose.

Purpose This systematic review and meta-analysis were performed to assess the efficacy and tolerability of chemotherapy in patients with advanced gastric cancer. Methods Randomized phase II and III clinical trials on first-line chemotherapy in advanced gastric cancer were identified by electronic searches of Medline, Embase, the Cochrane Controlled Trials Register, and Cancerlit; hand searches of relevant abstract books and reference lists; and contact to experts. Meta-analysis was performed using the fixed-effect model. Overall survival, reported as hazard ratio (HR) with 95% CI, was the primary outcome measure. Results Analysis of chemotherapy versus best supportive care (HR = 0.39; 95% CI, 0.28 to 0.52) and combination versus single agent, mainly fluorouracil (FU) -based chemotherapy (HR = 0.83; 95% CI = 0.74 to 0.93) showed significant overall survival benefits in favor of chemotherapy and combination chemotherapy, respectively. In addition, comparisons of FU/cisplatin-containing regimens with versus without anthracyclines (HR = 0.77; 95% CI, 0.62 to 0.95) and FU/anthracycline-containing combinations with versus without cisplatin (HR = 0.83; 95% CI, 0.76 to 0.91) both demonstrated a significant survival benefit for the three-drug combination. Comparing irinotecan-containing versus nonirinotecan-containing combinations (mainly FU/cisplatin) resulted in a nonsignificant survival benefit in favor of the irinotecan-containing regimens (HR = 0.88; 95% CI, 0.73 to 1.06), but they have never been compared against a three-drug combination. Conclusion Best survival results are achieved with three-drug regimens containing FU, an anthracycline, and cisplatin. Among these, regimens including FU as bolus exhibit a higher rate of toxic deaths than regimens using a continuous infusion of FU, such as epirubicin, cisplatin, and continuous-infusion FU.