Phase I/II trial of docetaxel plus oxaliplatin and 5-fluorouracil (D-FOX) in patients with untreated, advanced gastric or gastroesophageal cancer

Abstract

4612 Background: Docetaxel combined with cisplatin/5-fluouracil resulted in significantly longer time-to-progression and survival but also 30% rate of complicated neutropenia (JCO 2006; 24:4991). To improve the safety profile of docetaxel-based therapy, we studied docetaxel with oxaliplatin/5-fluorouracil (D-FOX) to establish the first-cycle MTD (phase II trial to follow). Methods: Patients with histologic proof of gastric or gastroesophageal adenocarcinoma with untreated stage IV cancer were eligible. ECOG PS of <2, near-normal organ function, and written consent were other eligibility criteria. The initial doses of oxaliplatin (85mg/m2) and 5-fluorouracil (2.2g/m2 as 48-hour infusion), given every 2 weeks, were kept constant. Docetaxel was started at 20mg/m2 (Level 1) every 2 weeks in a typical 3x3 phase I design. Subsequent levels (+5mg/m2 every 4 weeks) were added. Fatigue, incompletely treated nausea, and oxaliplatin/5-flurouracil-related toxicities were excluded to determine the MTD. Results: A total of 36 patients have been treated. Currently, docetaxel dose is 47.5mg/m2 every 2 weeks (Level 11). MTD was not reached at Level 10. Overall, grade 3 or 4 first-cycle toxicities have occurred in <5% of patients and without complicated neutropenia. Fifteen of 34 patients have had a confirmed partial response, 13 had stability, and 6 patients had progression. Conclusions: The MTD of D-FOX has not yet been established but its safety profile (D-FOX with 45mg/m2 of docetaxel every 2 weeks) is excellent and the regimen is quite active against untreated gastric or gastoresophageal cancer. Translation studies and additional clinical data will be presented. Supported in part by sanofi-aventis pharma. [Table: see text]