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Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis Based on Aggregate Data

Anna D. Wagner, Wilfried Grothe, Johannes Haerting, Gerhard Kleber, Axel Grothey, Wolfgang E. Fleig

From the First Department of Medicine, Coordinating Centre for Clinical Trials, Department of Medicine IV, and Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany; and Mayo Clinic College of Medicine, Rochester, MN

Address reprint requests to Anna D. Wagner, MD, First Department of Medicine, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str 40, 06120 Halle/Saale, Germany; e-mail: anna-dorothea.wagner{at}gmx.de

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.

Support for the Coordinating Centre for Clinical Trials, Halle, Germany by the German Ministry of Education and Research Grant No. BMBF/FKZ: 01GH0105 KKS, Halle, Germany.

Presented in part at the 6th International Gastric Cancer Congress, Yokohama, Japan, May 4-7, 2005; and the 13th European Cancer Conference, Paris, France, October 30-November 3, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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