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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis

The Gastric (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group.

Review published: 2010.

Link to full article: [Journal publisher]

CRD summary

The authors concluded that there was a modest increase in survival over five years in patients with gastric cancer for adjuvant fluorouracil chemotherapy compared with surgery alone. This conclusion reflected the evidence presented and is likely to be reliable. However, the other eligible chemotherapy regimens were indistinguishable from fluorouracil.

Authors' objectives

To evaluate the effectiveness of adjuvant chemotherapy for resectable gastric cancer.

Searching

MEDLINE (1970-2009), Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov were searched. Search terms were reported in supplementary online emethods (see URL for Additional Data). Proceedings and books from major oncological meetings were examined. Researchers were approached to identify unpublished trials. No language restrictions were applied.

Study selection

All randomised controlled trials (closed to recruitment before 2004) with individual patient data (IPD) comparing chemotherapy after resectable gastric cancer with surgery alone for overall survival and disease-free survival were eligible for inclusion. Overall survival was defined as the time from randomisation to mortality from any cause or to last follow up. Disease-free survival was calculated from time to relapse, second cancer, or mortality (whichever came first). Relevant chemotherapy regimens were classified as: mono-chemotherapy; fluorouracil and mitomycin C with anthracyclines; fluorouracil and mitomycin C and others without anthracyclines; and other poly-chemotherapy. Trials investigating immunotherapy or neoadjuvant or perioperative chemotherapy, radiotherapy or intraperitoneal chemotherapy were excluded.

Male patients predominated (over 60%), and most were aged between 50 and 59 years (29%). Dosages and schedules were variable in the different trials, as was cancer stage measured using the International Union Against Cancer staging tool. Patient characteristics were listed in separate supplementary online tables (see URL for Additional Data).

The authors did not state how many reviewers selected the studies.

Assessment of study quality

IPD were centrally re-analyzed. Inconsistencies in the data were checked; diagnostic tools for randomisation quality were systematically applied.

Data extraction

IPD were used to calculate hazard ratios (HR) and associated 95% confidence intervals (CI) based on intention-to-treat data. Attempts were made to obtain IPD data from all eligible trials, but were only provided for 17 of 31 trials.

Methods of synthesis

Overall survival and disease-free survival were analysed through log-rank tests with trial as a stratification factor using a fixed-effects model weighted by inverse variance. Heterogeneity was tested using X2 statistics and measured with I2. Pooled hazard ratios were calculated without adjustment for covariates. Statistically significant effects were interpreted in terms of increase in survival probability based on estimations of survival curves.

Subgroups analyses were conducted based on region (Europe, Asia, USA). Sensitivity analysis was used to derive an overall treatment effect in all eligible trials by pooling IPD data with aggregate summary data extracted from publications. Groups of chemotherapy regimen (monochemotherapy; fluorouracil and mitomycin C with anthracyclines; fluorouracil and mitomycin C and others without anthracyclines; other polychemotherapy) were analysed as subgroups and interaction tests performed.

Results of the review

Individual patient data (IPD) were obtained for 17 of 31 trials (3,838 patients of 6,390 potentially eligible patients). All trials were open without blinding procedures, but there were no reported inconsistencies in randomisation procedures and there was no difference in follow-up between trial arms.

Adjuvant chemotherapy was associated with a benefit in survival (HR 0.82, 95% CI 0.76 to 0.90) and disease-free survival (HR 0.82; 95% CI 0.75 to 0.90) compared with surgery alone. Five year overall survival increased from 49 to 55% with chemotherapy. Heterogeneity between trials was not statistically significant. No interactions between regimens were significant. The general conclusions and magnitude of treatment effect were unchanged by sensitivity analysis.

Authors' conclusions

Postoperative adjuvant fluorouracil-based chemotherapy was associated with reduced risk of death in patients with gastric cancer compared with surgery alone.

CRD commentary

The authors addressed a clear research question supported by unambiguous inclusion criteria. Several data sources (including electronic databases) were searched with no language restrictions. Researchers were contacted for unpublished information. Methods used to reduce error and bias during study selection were not reported, and the impact on review conclusions was unclear.

Data were checked for validity and consistency. Appropriate methods of pooling were utilised and heterogeneity was explored. However, the exploration of variation in the effectiveness of type of regimen found no significant interaction, which made the specific mention of fluorouracil regimen superfluous in the authors' conclusion. The comparison of different regimens may be sub-optimal in relation to mixed-treatment comparisons, which included additional information from trials that compared eligible treatments directly as well as placebo comparisons.

The authors' conclusion reflected the evidence presented and is likely to be reliable

Implications of the review for practice and research

Practice: The authors stated that postoperative adjuvant fluorouracil-based chemotherapy is recommended for patients who have not received perioperative treatments after complete resection of their gastric cancer.

Research: The authors did not state any implications for research.

Funding

Japan Clinical Research Support Unit (J-CRSU); Epidemiological and Clinical Research Information Network (ECRIN); Institut National du Cancer, France (INCa).

Bibliographic details

The Gastric (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA 2010; 303(17): 1729-1737. [PubMed: 20442389]

Indexing Status

Subject indexing assigned by NLM

MeSH

Antineoplastic Agents /therapeutic use; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Randomized Controlled Trials as Topic; Stomach Neoplasms /drug therapy /surgery; Survival Analysis; Treatment Outcome

AccessionNumber

12010002842

Database entry date

09/06/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 20442389