Phase I study of 3-weekly docetaxel, capecitabine and oxaliplatin combination chemotherapy in patients with previously untreated advanced gastric cancer.

PURPOSE: Adding docetaxel to cisplatin and 5-fluorouracil (5-FU) (DCF) significantly improved clinical efficacy in advanced gastric cancer (AGC). To further improve the efficacy and tolerability, we substituted oxaliplatin for cisplatin and capecitabine for 5-FU in the DCF regimen and performed a phase I study to determine the recommended dose (RD) and dose-limiting toxicity (DLT) of docetaxel, capecitabine and oxaliplatin (DXO) combination in patients with AGC.

MATERIALS AND METHODS: Previously untreated patients with histologically proven metastatic AGC and ECOG performance status 0-2 were enrolled. Docetaxel and oxaliplatin were administered i.v. on day 1. Capecitabine was administered orally bid on days 1-14. Each cycle was repeated every 3 weeks. DLTs were evaluated during the first two cycles of treatment.

RESULTS: Twenty-one patients were enrolled: 15 patients in dose-escalation phase and 6 patients in the extension at the RD. Median age was 50 years (range 21-65 years). At dose level 3 (60 mg/m(2) docetaxel, 1,000 mg/m(2) capecitabine, 100 mg/m(2) oxaliplatin), 1 diarrhea (DLT) was found among 6 patients while at dose level 4 (60 mg/m(2) docetaxel, 800 mg/m(2) capecitabine, 130 mg/m(2) oxaliplatin), 2 DLTs (febrile neutropenia and diarrhea) were observed among 3 patients. Therefore, the dose level 3 was determined as RD. DLTs include grade 3 diarrhea and febrile neutropenia. Cumulative (all cycles) grade 3/4 toxicity included neutropenia (75%), leucopenia (50%), febrile neutropenia (25%), diarrhea (17%), and neuropathy (17%). Of 14 patients with measurable lesions, 11 achieved partial response and 3 showed stable disease.

CONCLUSION: The RD of the DXO regimen in patients with AGC is capecitabine 1,000 mg/m(2) twice daily on days 1-14, in combination with docetaxel 60 mg/m(2) (day 1) and oxaliplatin 100 mg/m(2) (day 1) repeated every 3 weeks. The DXO regimen seems to have promising activity and offers an easy alternative to DCF. The toxicities appear to be still substantial, but manageable.