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New Single and Combination Drugs Showing Promise in Gastric Cancer: Presented at ESMO

By David J.E. Candlish

NICE, FRANCE -- October 20, 2002 -- A number of new agents are showing promise, either alone or as the basis of innovative combination therapies, in the palliative or perioperative treatment of gastric cancer, according to data presented at the 27^th Congress of the European Society for Medical Oncology.

Dr. Patrick Schoffski of the Medizinische Hochschule in Hannover, Germany, described how gastric cancer is still a major health problem around the world with no "gold standard" treatment available.

Only a few of the current chemotherapeutic agents provide active palliation in this disease area. Single-agent studies generally indicate an objective response rate of less than 20 percent, and responses are mainly partial and of limited duration. Even combination studies have failed to produce conclusive evidence of improved survival, and there is no consensus for standard chemotherapy for patients with advanced gastric cancer.

The obvious need for new agents to improve treatment options in this disease area has led to the intensive study of a number of new agents. These include the oral fluoropyrimidines, taxanes, and topoisomerase I inhibitors.

The oral fluoropyrimidines are prodrugs for 5-fluorouracil (5-FU). They have a long history of use for gastric cancer and other gastrointestinal tract malignancies in Japan, but have only recently been introduced in Western countries. This group includes combination drugs such as UFT and S-1, which are based on the oral 5-FU prodrug tegafur. UFT is a fixed combination of tegafur with uracil in a 4:1 ratio. Uracil acts as a competitive inhibitor of 5-FU degradation.

S-1 is another novel combination, consisting of tegafur with gimeracil and oteracil to inhibit 5-FU degradation.

Other compounds in the group, such as capecitabine and doxifluridine, are tumour activated. Capecitabine, in combination with CDDP (cisplatin), achieved an impressive 68 percent response rate in one study and merits further study.

The taxanes include the prototypical paclitaxel, which interferes with tubulin assembly, and docetaxel, which is derived from the European yew tree. Single-agent studies with paclitaxel have shown only modest results, but it shows promise in combination with 5-FU and other well-established agents.

The topoisomerase I inhibitors include irinotecan and rubetican. Irinotecan is a semisynthetic compound that has become a standard treatment in colorectal cancer. Used alone in gastric cancer it has only moderate activity, but in combination studies, response rates as high as 62 percent have been reported.

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