Chemotherapy of advanced gastric cancer

Summary

Gastric cancer is the second most frequent cancer in the world. Approximately 84% of patients with gastric cancer will have advanced disease and median survival of these patients without chemotherapy is only 3–4 months. “Classical” chemotherapy regimens, mainly CF (cisplatin plus infusional 5FU) and ECF (cisplatin plus infusional 5FU plus Epirubicin) obtain responses in 20–40% of the patients and improve quality of life. Nevertheless, duration of these responses is short with very few complete responses. Median time to tumor progression (TTP) with these regimens is only about 4–5 months and median survival does not exceed 7–10 months. Moreover, benefit seems to be limited to patients with good performance status and treatment toxicity and discomfort are not negligible, specially that of regimens with cisplatin or infusional 5FU. Trying to improve these results, the incorporation of new drugs has been explored. Among the new combinations, the more developed ones are those with Docetaxel (DCF), oxaliplatin (EOX, FLO), Capecitabine (EOX, cisplatin-Xeloda) and irinotecan (ILF). We have final results from Phase III trials that suggest that all these regimens could have a role in the treatment of these patients but survival is still very poor and toxicity remains important. It would be interesting to investigate other new combinations and the incorporation of drugs directed against new therapeutic targets in this setting. It would be of utmost interest that these clinical trials would also explore clinical and molecular prognostic and predictive factors.

Introduction

Gastric cancer is the second most frequent cancer in the world. In Europe, 95,000 new cases were diagnosed in the year 2000.¹ During that same year, 78,000 patients (83% of the incidence) died due to it. There has been a decrease in the incidence of distal gastric adenocarcinoma in the West in recent years. On the contrary, proximal and esophagogastric junction adenocarcinomas are increasing.

Advanced gastric cancer is considered to be that diagnosed as non-resectable disease, either because it is locally advanced (30% of the cases at diagnosis) or that presenting as metastatic disease (another 30%). Also included in this definition are cases of relapse after surgery (60% of the resected). Thus, overall, approximately 84% of patients with gastric cancer will have advanced disease. Even though metastatic, relapsed and locally advanced patients are often enrolled in clinical trials. The prognosis of the locally advanced cancer, although also bad, is slightly better; median survival of 7–10 months in relapsed or metastatic patients treated with chemotherapy and 12–15 months in the locally advanced in this setting. In this subgroup, some type of loco-regional radical treatment can be included, specially if there is a response after a systemic treatment. Thus, it would be best to avoid mixing both types of patients in the same trial or, at least, to analyze them separately.