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 F Grothey, Wolfgang E. Fleig

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2903-2909
Number of pages7
JournalJournal of Clinical Oncology
Volume24
Issue number18
DOIs
StatePublished - Jun 20 2006

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Fluorouracil
Stomach Neoplasms
Meta-Analysis
Drug Therapy
irinotecan
Cisplatin
Anthracyclines
Survival
Drug Combinations
Reference Books
Epirubicin
Phase III Clinical Trials
Phase II Clinical Trials
Poisons
Combination Drug Therapy
Randomized Controlled Trials
Outcome Assessment (Health Care)
Mortality
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wagner, A. D., Grothe, W., Haerting, J., Kleber, G., Grothey, A. F., & Fleig, W. E. (2006). Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data. Journal of Clinical Oncology, 24(18), 2903-2909. https://doi.org/10.1200/JCO.2005.05.0245

Chemotherapy in advanced gastric cancer : A systematic review and meta-analysis based on aggregate data. / Wagner, Anna D.; Grothe, Wilfried; Haerting, Johannes; Kleber, Gerhard; Grothey, Axel F; Fleig, Wolfgang E.

In: Journal of Clinical Oncology, Vol. 24, No. 18, 20.06.2006, p. 2903-2909.

Research output: Contribution to journalArticle

Wagner, AD, Grothe, W, Haerting, J, Kleber, G, Grothey, AF & Fleig, WE 2006, 'Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data', Journal of Clinical Oncology, vol. 24, no. 18, pp. 2903-2909. https://doi.org/10.1200/JCO.2005.05.0245
Wagner, Anna D. ; Grothe, Wilfried ; Haerting, Johannes ; Kleber, Gerhard ; Grothey, Axel F ; Fleig, Wolfgang E. / Chemotherapy in advanced gastric cancer : A systematic review and meta-analysis based on aggregate data. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 18. pp. 2903-2909.
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abstract = "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.",
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