Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen)

Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m² (3 patients), 65 mg/m² (6 patients), and 75 mg/m² (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m² (grade 4 leukopenia) and in 3 patients at 75 mg/m² (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m², d 1; leucovorin 200 mg/m², 2 h, d1–2; 5-fluorouracil 400 mg/m², iv, d 1–2 and 600 mg/m² civ, 22 h, d 1–2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.