Combination chemotherapy shows small survival benefit in advanced stomach cancer

Patients with advanced stomach cancer have the best chance of prolonging their survival with a combination of chemotherapies instead of just one, according to a new review of previous studies.

The review also concludes that the best combination is 5-FU, one of the oldest and most commonly used chemotherapy drugs, along with powerful antibiotics called anthracyclines and a platinum-based drug called cisplatin. The benefit, however, is small and may cause a patient to experience more discomfort from the higher toxicity.

The review was conducted by Dr. Anna Dorothea Wagner of the Martin-Luther-University Halle-Wittenberg in Germany and colleagues. It appears in the April issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Despite recent progress, stomach cancers remain the second highest cause of cancer death worldwide, in large part because the majority of stomach cancer patients are diagnosed at a late stage of the disease when tumors are inoperable. Although small tumors can be surgically removed in the earliest stages of the disease, the only cure for advanced stomach cancer is complete removal of the stomach.

When Wagner and colleagues compared survival rates among 1,338 patients receiving combination versus single-drug care, they found that half the patients receiving combination treatment were still living seven months later, while half of those taking a single drug were still living 5.9 months later. Most of the patients in the studies were age 56 to 64.

Combination therapies were more toxic than single-drug therapies, however, so “it remains an open question, whether the benefit in survival does indeed compensate for the burden of additional toxicity to be endured by the patient,” Wagner says.

The overall rate of toxic deaths among the studies was 2.1 percent for combination chemotherapy and 0.9 percent for single-drug therapy, according to the Cochrane researchers.

Although nine of 10 relevant studies did not demonstrate a significant benefit in overall survival for the combination chemotherapy, powerful statistical analysis did “demonstrate a small but statistically significant and consistent benefit for the combination versus single agent therapy in terms of over overall survival,” the reviewers conclude.

For those whom the three-drug therapy is recommended, the review found that large single doses of 5-FU were more likely to cause death than gradual intravenous administration.

Combination chemotherapy is used on a variety of cancers, from lung cancer to endometrial cancers, and combination therapy is the preferred treatment for advanced stomach cancer in the United States and Europe, according to Wagner. Yet combination therapy for stomach cancer “is regarded as controversial in Japan,” where most physicians rely on single-drug therapy, Wagner says.

In the United States, the prevalence of cancers at the junction between the stomach and the esophagus, the muscular tube that feeds food to the stomach, is increasing, perhaps in part due to an increase in chronic acid reflux disease, Wagner says.

“Early diagnosis of gastric cancer is difficult because most patients are asymptomatic in the early stage,” says Dr. Peter Lopez, a clinical professor and surgeon and the University of Miami School of Medicine. “Weight loss and abdominal pain often are late signs of tumor progression,”

In the next Cochrane review of advanced stomach cancer treatments, scheduled for 2006, researchers will examine the effects of anticancer therapies still in clinical trials that specifically target stomach cancer cells.

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