Purpose: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of modified FLOT regimen (fluorouracil plus leucovorin, oxaliplatin and docetaxel) for treating Chinese patients with metastatic adenocarcinoma of stomach.
Methods: Chinese patients with untreated advanced or metastatic stomach adenocarcinoma were enrolled. Docetaxel (D), oxaliplatin (O) and leucovorin were administrated intravenously on day 1. Fluorouracil (F) was administrated continuous intravenously on day 1 for 48 h. The treatment was repeated every 2 weeks. The start doses of docetaxel and oxaliplatin were 40 mg/m2 and 65 mg/m2, respectively. Dose escalation followed a 3 + 3 design. Total 6 dose levels were set to determine the MTD and RD. Fluorouracil and leucovorin were given as fix doses at 2200 mg/m2 and 200 mg/m2, respectively. Adverse events that occurred in the first 2 cycles were recorded to determine dose-limiting toxicity (DLT). The primary endpoints were MTD and RD determination.
Results: A total of 18 patients were treated in 5 dose levels. DTL occurred in one patient of level 4 (grade 3 hypophosphatemia). Other 3 patients were enrolled in level 4 and no DLTs were observed. In level 5, 2 patients suffered grade 4 neutropenia after first cycle of treatment and were defined as DLTs. Therefore, level 5 (D/O/F: 50/75/2200 mg/m2) was defined as MTD and level 4 (D/O/F: 45/75/2200 mg/m2) was defined as RD. Common adverse events in first two cycles were nausea, anorexia, leukopenia, neutropenia and anemia. For 16 patients assessable for tumor response, 7 patients had partial response (43.7%) and 5 experienced stable disease. Disease control rate were 75% (12/16). Two patients underwent conversion operation after 6 cycles of treatment. One pathological complete response (case in level 3) and one pathological partial response (case in level 2) were observed. Median progression-free survival was 4.4 months (95% CI 2.9-5.9 months) in 14 patients.
Conclusions: The RD of modified FLOT regimen in Chinese patients with advanced gastric cancer was docetaxel 45 mg/m2, oxaliplatin 75 mg/m2, leucovorin 200 mg/m2 and fluorouracil 2200 mg/m2 on day 1 of every 14-day cycle. Its efficacy will be assessed by further phase II study.
Keywords: 5-Fluorouracil; Docetaxel; Dose-finding; Gastric cancer; Oxaliplatin.