Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long-Term Follow-Up.

Lessons Learned: Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three-drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting.The DOF regimen represents an alternative to the FLOT (5-FU 2,600 mg/m as 24-hour infusion with leucovorin 200 mg/m, oxaliplatin 85 mg/m, and docetaxel 50 mg/m) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting.

Background: The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum-taxane-fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5-FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Methods: Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m on day 1, oxaliplatin 85 mg/m on day 1, and 5-FU 2,400 mg/m continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR).

Results: Forty-four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2% (68.3% partial response; 4.9% complete response). Therapy was discontinued for progressive disease in 53%, toxicity in 26%, and death on treatment in 16%. Two patients underwent surgical resection. Thirty-three patients (76.7%) received at least seven cycles (7-34). Grade 3-4 toxicities occurred in 31 patients (72.1%), including neutropenia (23.3%), neurologic (20.9%), and diarrhea (14.0%). Median overall survival was 10.3 months.

Conclusion: DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.