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Treatment of Advanced Gastric Cancer: Where We Are in 2003

The issue of the effectiveness of systemic chemotherapy in metastatic gastric carcinoma engendered considerable debate during the late 1980s and early 1990s. Substantial scepticism existed as to whether or not chemotherapy had any advantages over best supportive care for patients with advanced gastric cancer. Four randomised trials have been reported that have addressed this issue using a randomisation of chemotherapy versus best supportive care. The data generated were rather consistent: chemotherapy improved median survival from 3 to 7 months [1, 2]. These results strongly supported the use of chemotherapy in patients with metastatic gastric carcinoma, however, problems remain when defining the standard of care. Different combinations of 5-FU, adriamycin, methotrexate, cisplatin and etoposide had given promising results. The first protocol which was considered as a standard of care was the FAMTX (5-FU + adriamycin + high dose methotrexate). This protocol was shown to give better results than the FAM protocol (5-FU + adriamycin + mitomycin C) in terms of response rate and survival. During the same period of time, two other active protocols were developed: combination of continuous infusion of 5-FU (5 days) + cisplatin (FP), and combination of 5-FU, etoposide and leucovorin (ELF). A large trial of the EORTC compared these different regimens. This trial gave very disappointing results with less than 25% of objective response rates in either of the three arms and no difference in terms of overall survival or toxicity [3]. A more recent British protocol used continuous infusion of 5-FU + cisplatin + epiadriamycin (ECF) and gave better results than FAMTX with no difference in terms of quality of life [4]. Consequently, the situation of first-line chemotherapy in gastric carcinoma remains a little bit confused and we are now waiting for the results of large phase III trials evaluating new agents such as irinotecan combined with 5-FU [5] or docetaxel + cisplatin [6]. The results of these two trials will be presented during the next meeting of the American Society of Clinical Oncology.