Chemotherapy for advanced gastric cancer

Of all patients with gastric cancer 80% to 90% are either diagnosed at an advanced stage when the tumour is inoperable, or develop a recurrence within five years after surgery. Chemotherapy clearly improves survival in comparison to best supportive care only. In addition, combination chemotherapy further improves survival compared to single-agent 5-FU. However, combination chemotherapies have higher rates of adverse effects, and their impact on the patient's quality of life has not been adequately studied. 5-FU/platinum combinations, with or without an anthracycline, as well as irinotecan and docetaxel-containing combinations are reasonable current treatment options.

Authors' conclusions: 

Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU. All patients should be tested for their HER-2 status and trastuzumab should be added to a standard fluoropyrimidine/cisplatin regimen in patients with HER-2 positive tumours. Two and three-drug regimens including 5-FU, cisplatin, with or without an anthracycline, as well as irinotecan or docetaxel-containing regimens are reasonable treatment options for HER-2 negative patients.

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Background: 

Gastric cancer currently ranks second in global cancer mortality. Most patients are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. Apart from supportive care and palliative radiation to localized (e.g. bone) metastasis, systemic chemotherapy is the only treatment option available in this situation.

Objectives: 

To assess the efficacy of chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapy regimens in advanced gastric cancer.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE up to March 2009, reference lists of studies, and contacted pharmaceutical companies and national and international experts.

Selection criteria: 

Randomised controlled trials on systemic intravenous chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapies in advanced gastric cancer.

Data collection and analysis: 

Two authors independently extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information.

Main results: 

Thirty five trials, with a total of 5726 patients, have been included in the meta-analysis of overall survival. The comparison of chemotherapy versus best supportive care consistently demonstrated a significant benefit in overall survival in favour of the group receiving chemotherapy (hazard ratios (HR) 0.37; 95% confidence intervals (CI) 0.24 to 0.55, 184 participants). The comparison of combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (HR 0.82; 95% CI 0.74 to 0.90, 1914 participants). The price of this benefit is increased toxicity as a result of combination chemotherapy. When comparing 5-FU/cisplatin-containing combination therapy regimens with versus without anthracyclines (HR 0.77; 95% CI 0.62 to 0.95, 501 participants) and 5-FU/anthracycline-containing combinations with versus without cisplatin (HR 0.82; 95% CI 0.73 to 0.92, 1147 participants) there was a significant survival benefit for regimens including 5-FU, anthracyclines and cisplatin. Both the comparison of irinotecan versus non-irinotecan (HR 0.86; 95% CI 0.73 to 1.02, 639 participants) and docetaxel versus non-docetaxel containing regimens (HR 0.93; 95% CI 0.75 to 1.15, 805 participants) show non-significant overall survival benefits in favour of the irinotecan and docetaxel-containing regimens.

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