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Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer A Meta-analysis

The GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group*
JAMA. 2010;303(17):1729-1737. doi:10.1001/jama.2010.534.
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Context Despite potentially curative resection of stomach cancer, 50% to 90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) have compared surgery alone with adjuvant chemotherapy, but definitive evidence is lacking.

Objectives To perform an individual patient-level meta-analysis of all RCTs to quantify the potential benefit of chemotherapy after complete resection over surgery alone in terms of overall survival and disease-free survival, and to further study the role of regimens, including monochemotherapy; combined chemotherapy with fluorouracil derivatives, mitomycin C, and other therapies but no anthracyclines; combined chemotherapy with fluorouracil derivatives, mitomycin C, and anthracyclines; and other treatments.

Data Sources Data from all RCTs comparing adjuvant chemotherapy with surgery alone in patients with resectable gastric cancer. We searched MEDLINE (up to 2009), the Cochrane Central Register of Controlled Trials, the National Institutes of Health trial registry, and published proceedings from major oncologic and gastrointestinal cancer meetings.

Study Selection All RCTs closed to patient recruitment before 2004 were eligible. Trials testing radiotherapy; neoadjuvant, perioperative, or intraperitoneal chemotherapy; or immunotherapy were excluded. Thirty-one eligible trials (6390 patients) were identified.

Data Extraction As of 2010, individual patient data were available from 17 trials (3838 patients representing 60% of the targeted data) with a median follow-up exceeding 7 years.

Results There were 1000 deaths among 1924 patients assigned to chemotherapy groups and 1067 deaths among 1857 patients assigned to surgery-only groups. Adjuvant chemotherapy was associated with a statistically significant benefit in terms of overall survival (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.90; P < .001) and disease-free survival (HR, 0.82; 95% CI, 0.75-0.90; P < .001). There was no significant heterogeneity for overall survival across RCTs (P = .52) or the 4 regimen groups (P = .13). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy.

Conclusion Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone.

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Figure 1. Study Flowchart
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Figure 2. Individual Trial and Overall Hazard Ratio for Overall Survival When Comparing Any Adjuvant Chemotherapy vs Surgery Alone
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The inverse of the variance of observed events minus expected events measures the weight of each trial in the analysis. P values are from P-for-effect modification testing for heterogeneity within or across the groups of regimens. The sizes of data markers are proportional to the number of deaths in the trials. CI indicates confidence interval; HR, hazard ratio.

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Figure 3. Overall Survival Estimate After Any Chemotherapy or Surgery Alone Truncated at 10 Years
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The estimates of the survival curves use an actuarial approach as described in the Methods.

Place holder to copy figure label and caption
Figure 4. Individual Trial and Overall Hazard Ratio for Disease-Free Survival When Comparing Any Adjuvant Chemotherapy vs Surgery Alone
Graphic Jump Location

The inverse of variance of observed events minus expected events measures the weight of each trial in the analysis. P values are from P-for-effect modification testing for heterogeneity within or across the groups of regimens. The sizes of the data markers are proportional to the number of events. CI indicates confidence interval; HR, hazard ratio.

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