Background: To study in a phase I-II trial the maximum tolerated dose, the toxicity, and the tolerance of adding radiotherapy to systemic chemotherapy administered preoperatively in patients with locoregionally advanced gastric adenocarcinoma.
Patients and methods: Patients with adenocarcinoma of the stomach (T(3)(-)(4)N(any) or T(any)N+), performance status </=1, normal hematological, hepatic and renal functions received two cycles of cisplatin 100 mg/m(2) on day 1, 5-FU 800 mg/m(2) on days 1 to 4 and leucovorin 60 mg b.i.d. on days 1 to 4 q3w, concomitantly with radiation therapy escalated in three dose tiers (31.2, 38.4 and 45.6 Gy).
Results: Nineteen patients were accrued and 18 completed neoadjuvant therapy. Major toxicity consisted of grade 3/4 leucopenia and mucositis in 89% and 36% of the patients, respectively. Only one episode of febrile neutropenia was recorded. Dose level number 2 (38.4 Gy) with the chemotherapy given q4w is the recommended dose level. All patients were subsequently operated and no fatalities occurred. Pathological assessment showed one complete and eight partial responses. Two- and 3-year relapse-free survival rates were 57% and 50%, respectively. Only one patient relapsed locally. The peritoneum was the most frequent site of relapse.
Conclusions: This neoadjuvant therapeutic program is relatively well tolerated, does not seem to increase the operative risk, and might increase the locoregional control of the disease. The frequency of peritoneal involvement in relapsing patients underscores the need for a more effective systemic treatment.