Status of treatment for advanced gastric carcinoma

Gastric cancer is the second most common cause of cancer death worldwide. Advanced gastric cancer is incurable. The most widely investigated single-agent chemotherapy is 5-fluorouracil (5-FU), with partial response rates up to 20%. Pilot phase II studies investigating combinations of 5-FU, anthracyclines, mitomycin, methotrexate, and platinums achieved higher response rates; however, the response rates declined in subsequent larger trials. Furthermore, toxicity was substantially higher in confirmatory trials, emphasizing the need to develop well-tolerated regimens prior to multi-institutional testing. Although phase III studies of combination regimens have not achieved a clear worldwide standard, the regimen of epirubicin, cisplatin, and continuous-infusion 5-FU achieved a survival benefit, possibly through the increased activity of infusional 5-FU combined with cisplatin. The taxanes, irinotecan and oxaliplatin, have recently shown important activity in gastric cancer. Patient accrual to a phase III trial comparing a docetaxel-based combination regimen with the regimen of cisplatin and 5-FU has completed accrual. Whether patients with adenocarcinomas of the proximal stomach and gastroesophageal junction will have the same response rates to these new agents as did patients with classical body and distal gastric cancers is unknown. It is anticipated that the development of these active new agents will ultimately improve survival for patients with advanced gastric cancer.