London Friday April 7 2006- Despite not being recognized as one of the ‘big four’ cancer types- breast, prostate, lung and colorectal cancer- approximately 196,000 new cases of gastric cancer will be diagnosed in the seven major markets* in 2006, 56% of which will be in Japan. Globally, 930,000 new cases of gastric cancer are diagnosed each year, with 700,000 people dying of the disease. While the incidence of gastric cancer is declining, lack of appropriate screening techniques in most western countries means that when it is diagnosed, it is advanced and as such very difficult to treat. However, according to a new report from independent market analyst Datamonitor** (DTM.L), the results of a recent clinical trial could provoke a shift in current treatment recommendations.

Less bad food, more good

The incidence of gastric cancer is declining the world over, largely because of advances in food preservation and storage- mainly refrigeration- which has resulted in a lower intake of salted, smoked and pickled foods, and a greater availability of fresh fruits and vegetables. Thus, the epidemiology of gastric cancer varies widely by geographic region and race.

Despite a population nearly half the size, incidence of gastric cancer in Japan is nearly five times that in the US, which has the second highest incidence of the seven major pharmaceutical markets. On a global scale, incidence of gastric cancer is highest in Asia, Eastern Europe, South America and developing countries. This is in part due to a high incidence of H. pylori infection in these areas, a known human carcinogen with a strong association in the development of gastric cancer, says Datamonitor oncology analyst Fleur Pijpers. "In Asia, Eastern Europe and developing countries, the consumption of salts, nitrates and smoked or pickled foods is significantly higher than in the US and Western Europe. These are known risk factors for gastric cancer, resulting in a higher incidence of the disease in these regions."

In high-incidence areas, mass routine screening is a viable option and therefore more effective than in western countries. As a result, the majority of gastric cancer cases in Japan are diagnosed at an early stage when curative therapy is possible. However, because of this high incidence and need for surgery, an enormous burden is placed on healthcare services. Conversely, routine screening for gastric cancer is not carried out in the US and western Europe, due to a lack of effectiveness resulting from low incidence rates. Consequently, the majority of patients in these areas present with advanced disease, which is associated with poor survival and a resulting higher mortality.

The incorporation of neoadjuvant therapy into treatment guidelines is likely to be the next major change to occur in the gastric cancer treatment market. Although still experimental, neoadjuvant therapy is administered before a patient has surgery and has a number of theoretical advantages over adjuvant therapy. Neoadjuvant therapy has significant antitumor activity, meaning that unresectable tumors (those that cannot be surgically removed) can be down-staged and rendered resectable, thus facilitating subsequent treatment and improving overall prognosis.

Because neoadjuvant therapy is administered before surgery, patients will have a better overall physical and nutritional status than is possible following a major operation. Therefore, patients are more likely to tolerate aggressive chemotherapy and/or radiotherapy than those who have been weakened by surgery, Pijpers says. "Adjuvant (after surgery) therapy regimens often require dosage adjustments and in those cases where the patient completes treatment, delays are frequent. Postoperative morbidity can often result in weight loss of up to 10% in more than 30% of patients, which precludes the administration of adjuvant therapy."

Results from the recently completed MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) trial have further highlighted the potential of neoadjuvant therapy. The MAGIC trial was the first well powered, randomized Phase III clinical trial to demonstrate the safety and feasibility of administering both neoadjuvant and adjuvant chemotherapy to patients. Opinion leaders interviewed by Datamonitor were enthusiastic that neoadjuvant therapy would eventually become part of standard treatment guidelines for gastric cancer.

The MAGIC trial, involving, the administration of neoadjuvant therapy to 503 patients with gastrointestinal tumors, 74% of whom had gastric cancer resulted in a greater percentage of curative resections and fewer incidences of palliative surgery, than those that received surgery alone.

However, of most significance in the MAGIC trial was the statistically significant improvement in survival rates and median overall survival, indicating that this modality is effective in the treatment of gastric cancer, Pijpers says. "Five-year survival and median overall survival was 36% and 24 months respectively in the neoadjuvant therapy arm, compared with 23% and 20 months in the surgery alone arm. The researchers therefore concluded that neoadjuvant chemotherapy significantly increases resectability, progression-free survival and overall survival in operable gastric cancer."

Recently, Sanofi-Aventis’ Taxotere (docetaxel) received approval from the US FDA for the first-line treatment in combination with cisplatin and 5-fluorouracil of advanced gastric cancer, becoming the first formal approval for this indication in the US since 1970. Taxotere is already approved in Japan and is also currently under evaluation by the EMEA as a potential treatment for gastric cancer in Europe, although a positive opinion recommending it for approval was also stated in March 2006, Pijpers says.

 "Despite the seemingly positive clinical trial data and approval from the FDA, Taxotere may not create as large an impact in the treatment of gastric cancer as expected. The survival benefit conferred by Taxotere amounts to only 2.5 weeks, which some believe does not offset its increased toxicity."