Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies

Background: Oxaliplatin, gemcitabine and capecitabine are all active agents against upper gastrointestinal and pancreaticobiliary cancers. Patients and methods: Patients with upper gastrointestinal malignancies treated with 0-2 prior chemotherapy regimens received oxaliplatin (85-100 mg/m²) as a 2-h i.v. infusion with gemcitabine (800-1000 mg/m²) at a constant rate i.v. infusion (CI) of 10 mg/m²/min on days 1 and 15 of a 28-day cycle. Capecitabine (600-800 mg/m²) was administered orally twice a day on days 1-7 and 15-21. A three per cohort dose escalation schema was used to determine the maximum tolerated dose (MTD) and the dose-limiting toxic effects (DLTs) of this combination regimen. Results: Thirty patients with advanced upper gastrointestinal malignancies were enrolled. The MTD was defined as oxaliplatin 100 mg/m² i.v. over 2 h plus gemcitabine 800 mg/m² i.v. at a CI of 10 mg/m²/min on days 1 and 15 with capecitabine 800 mg/m² p.o. b.i.d. days 1-7 and 15-21 of a 29-day cycle. DLTs include grade 3 fatigue and grade 3 dyspnea. One complete and two partial responses were observed. Conclusions: This biweekly schedule of oxaliplatin, gemcitabine and capecitabine is tolerable and warrants further investigation in biliary and pancreatic malignancies.