Modified FOLFOX in combination with docetaxel for patients with metastatic adenocarcinoma of the stomach or gastroesophageal junction: A multicenter phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Abstract

4545 Background: The combination of docetaxel, cisplatin, and fluorouracil (DCF) is clearly superior to CF in the treatment of patients (pts) with advanced gastric cancer (AGC). DCF is, however, associated with significant toxicity, including neutropenia, febrile neutropenia, diarrhea and mucositis. This study evaluated a biweekly, oxaliplatin-based modification of DCF. Methods: Pts with measurable, locally advanced or metastatic adenocarcinoma of the stomach or GE-junction and no prior chemotherapy received mFOLFOX (oxaliplatin 85 mg/sqm, leucovorin 200 mg/sqm, and fluorouracil 2.6 g/sqm via 24hr infusion) in combination with docetaxel 50 mg/sqm on day 1 every 2 weeks (FLOT-regimen). Prophylactic G-CSF was not administered. Overall response rate (RR) was the primary endpoint (power 80% to detect a RR of >40%) and toxicity profile the main secondary endpoint. The study was externally monitored according to GCP and data were reviewed by an independent safety board. Results: 59 pts (male, 41; female, 18) were enrolled. At the time of analysis, 53 pts were evaluable for toxicity and 51 pts for response. Median age was 60 (range, 29–76), median ECOG PS was 1, and almost all (93%) pts had metastatic disease. Of 51 pts, 2 had a CR and 25 pts attained a PR, adding to an overall RR of 53% (ITT-analysis). Stable disease was observed in 12 (23.5%) and progressive disease in 6 (11.8%) pts. Six (11.8%) pts were not evaluable for response. NCI-CTC grade 3 or 4 hematologic toxicity included leukopenia in 12 (22.6%), neutropenia in 23 (43%), and anemia in 2 (3.8%) pts. Febrile neutropenia was observed in 1 (1.9%) pt only. Other grade 3 or 4 toxicities included peripheral neuropathy in 4 (7.5%), nausea in 3 (5.7%), vomiting in 2 (3.8%) as well as diarrhea and fatigue in 5 (9.4%) pts each. No treatment related deaths were observed. Conclusions: FLOT is active and has a favorable toxicity profile in the treatment of pts with AGC. It may show activity also in perioperative treatment settings and may be considered as a useful treatment option for elderly pts. Survival data will be presented at the meeting. [Table: see text]