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Expert Critique

FROM THE ASCO Reading Room

Melinda Engevik, PhD Postdoctoral Fellow Baylor College of Medicine

Chronic intractable vomiting is a pressing health concern for approximately 3% of the population and is commonly associated with gastroparesis. The current medications used to treat chronic nausea and vomiting include antiemetic agents, neuromodulators, and prokinetic drugs. However, some patients are refractory to medication.

Gastric electrical stimulation (GES) has been proposed to treat patients who fail to respond to medical therapy. GES has been used for more than a decade to treat gastroparesis. Many studies have reported an improvement of symptoms, quality of life, and nutritional status in gastroparesis patients, but the data are less clear for patients with chronic intractable vomiting. In the highlighted study, only 30.6% of study participants reported improvement in vomiting frequency. This low percentage of patients reporting improvement calls into question the cost-effectiveness of GES for the treatment of chronic intractable vomiting. The current cost of GES treatment is around $30,000 USD. The average battery life of GES devices is approximately 5-10 years, and the GES device must be replaced after the battery is depleted. Additionally, device-related adverse events such as dislodgements and migration of the implantation site, hematoma, and implant site infection have been reported.

Since the individual response to GES is difficult to predict, GES treatment for vomiting requires further investigation and more studies are needed to identify predictive factors of favorable response. If these factors were known and could be used to delineate patients that would benefit, GES might become a common cost-effective treatment for chronic intractable vomiting. Consequently, it may be some time before GES is a recognized treatment strategy for these patients.

Full Critique

Chronic intractable vomiting is one of gastroenterology's most, with considerable financial, emotional, and quality-of-life consequences for patients. Still poorly understood, the condition presents a when low-fat, high-fiber diets and medications such as antidepressants and prokinetics fail to improve symptoms. Impaired nutritional status and weight loss may result.

Nausea occurring at least once a week has been observed in approximately 3% of the general population, while vomiting at least monthly without an underlying organic cause is reported by 2% of women and 3% of men. Interestingly, among patients with typical symptoms suggestive of gastroparesis, delays in stomach emptying are detected in only undergoing gastric scintigraphy.

Gastric electrical stimulation (GES) is a therapeutic option for refractory vomiting, with or without gastroparesis, but trials have yielded and placebo responses and cognitive influences have affected outcomes.

Most open-label cohort studies have reported that GES relieved nausea and vomiting. "Whether this is related to a placebo effect has not yet been firmly ruled out," said Guillaume Gourcerol, MD, of Rouen University Hospital in France, in an interview with the Reading Room. Gourcerol coauthored a study on a recent large, multicenter, randomized, double-blind trial of cross-over design published in

Up until now, GES efficacy has been studied in only three small randomized controlled trials that compared patients with their implanted stimulator turned either on or off in double-blind fashion, Gourcerol explained. Two of these trials were negative, while the third was positive in a post-hoc analysis.

Against that background, Gourcerol's team initiated the four-months-on, four-months-off study of 172 patients, in which high-frequency GES significantly reduced the occurrence of severe refractory vomiting and nausea in both diabetic and non-diabetic patients, with or without gastroparesis. In the face of nutritional deficiency, the only other options for these medically refractory patients were nasojejunal tube feeding or jejunostomy.

During the active "on" phase of GES, 30.6% of study patients reported at least a one-point improvement on a newly developed vomiting frequency scale versus 16.5% of patients during the "off" period, dropping from several episodes a day to fewer than one per week. "Therefore, this therapy can be offered to patients after failure of standard care," Gourcerol told the Reading Room. More than half of patients, however, reported no change in symptoms, suggesting that not all will benefit.

By way of mechanism, previous studies hypothesized that GES could restore the activity of the natural gastric pacemaker, Gourcerol explained, but in the present study it had no effect on gastric electrical activity or motility. "The efficacy of GES is therefore unrelated to acceleration of the gastric emptying rate, and some studies have suggested that the clinical efficacy is more related to a 'sensitivity effect.' By increasing the discomfort threshold for gastric distension, it prevents vomiting by allowing patients to better tolerate their food after a meal."

The study suggested that GES can help symptomatic patients without gastric motility disorders, and hence should not be restricted to patients with gastroparesis, Gourcerol said. In the U.S., however, GES is FDA approved only for gastroparesis, and the technique is expensive, including the device, surgery, and hospitalization. Offsetting these concerns, a recent French study suggested that the technique is cost-effective over the long-term, decreasing the direct and indirect costs of intractable nausea and vomiting by the equivalent of $3,000 to $5,000 per patient per year, he said. Another cost-effectiveness analysis on GES in diabetes patients with gastroparesis by found that GES reduced days in hospital by 61% in the first year, with the treatment emerging as cost-effective at the two-year horizon.

Stressing that the study was carried out in severely refractory patients "at the end of the road" of medical management, Gourcerol's group wrote, "The present results make sense in terms of clinical care, showing that a limited number of medically resistant patients may benefit from GES to relieve nausea and vomiting."

The authors cautioned, however, that more studies are needed to identify predictive factors of favorable response and to determine the technique's cost-effectiveness.