NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma.

Abstract

4072 Background: The rationale of the NeoFLOT-trial was the intensification of neoadjuvant chemotherapy (NACT) by prolongation of preoperative treatment. This strategy is based on the notion that while perioperative treatment is notably beneficial in locally advanced gastroesophageal cancer (GEC), postoperative chemotherapy can only be applied in a fraction of patients (pts). Methods: Pts with T3, T4 and/or N+ adenocarcinoma (GEC) were eligible for this multicenter phase II trial. NACT consisted of 6 cycles of oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, fluorouracil 2600 mg/m2 and docetaxel 50 mg/m2 (FLOT) applied q 2 wks. Staging was performed after 3 cycles to select pts with progressive disease (PD) for immediate surgery. Primary endpoint was the R0-resection rate. Secondary endpoints included the pathological complete response rate (pCR), histologic tumor regression grade (Becker 2003), safety, and progression-free survival (PFS). Results: From 10/2009 to 06/2011, 59 pts were enrolled of whom 58 pts were assessable for safety. Median age was 61 years (range: 32-79), 58.6% (34/58) had tumors of the gastroesophageal junction. 50 pts underwent surgery and were assessable for the primary endpoint. R0-resection rate was 86.0% (43/50). pCR was achieved in 20.0% (10/50) of pts. During NACT, 6.9% (4/58) of pts developed progressive disease. Dose reduction was performed in 43.1% (25/58) of pts resulting in a median dose intensity of 89.2%. Grade 3/4 neutropenia was observed in 29.3% (17/58) of pts, febrile neutropenia grade 3/4 in 1.7% (1/58). Common grade 3/4 non-hematologic adverse events were diarrhea (13.8% (8/58)) and mucositis (6.9% (4/58)). Treatment related mortality was 3.4% (2/58) with 2 cases of sepsis. After a median follow-up of 9.1 months, median PFS and OS have not been reached. Conclusions: These data indicate that NACT with 6 cycles FLOT is well-tolerated and highly effective in resectable GEC.