Phase I study of docetaxel, oxaliplatin and capecitabine (TEX) as first line therapy to patients with advanced gastro-oesophageal cancer.

BACKGROUND: ECF (epirubicin, cisplatin, 5-FU) has been a standard first-line regimen in patients with advanced gastro-esophageal cancer (GEC). If cisplatin is substituted by oxaliplatin (Eloxatin®) - E) and 5-FU by capecitabine (X - Xeloda®) this regimen is easily administered with at least comparable efficacy and lower toxicity. Recent studies indicate that efficacy can be improved by adding docetaxel (Taxotere® - T) to CF. We initiated a phase I trial of T, short-time infusion of E and continuously X (TEX) as first-line therapy in GEC to establish the recommended dose (RD) for further therapy.

MATERIALS AND METHODS: Patients were enrolled in cohorts of three at five dose levels. Patients had histologically confirmed GEC adenocarcinoma. Therapy was administered day 1 with escalating doses of docetaxel (60 mg/m² to 75 mg/m² iv as a 60 minutes infusion), oxaliplatin (85 to 130 mg/m² iv as a 30 minutes infusion) and oral capecitabine (1 000 to 1 250 mg/m²/day). TEX was repeated every third week for a maximum of eight cycles. Toxicity was evaluated according to CTCAE v3.0 and dose limiting toxicity (DLT) was evaluated after the first course of TEX.

RESULTS: From June 2007 to April 2009, 23 consecutive patients received TEX. At dose level V, two of four patients experienced DLT and therefore we included additional seven patients at dose level IV. Only one of seven experienced DLT but dose-intensity was reduced to 75% in four of seven patients after three courses of TEX. Therefore we defined dose level III as RD. Efficacy was promising with response rate 38%, PFS 9.4 months and OS 12.5 months.

CONCLUSION: The recommended dose of TEX (docetaxel 60 mg/m² iv day 1, oxaliplatin 115 mg/m² iv day 1 and oral capecitabine 1250 mg/m²/day continuously) every three weeks is easily administered in an out-patient setting. Efficacy is promising and will be evaluated in a phase II study.