A randomized phase II study of leucovorin, 5-fluorouracil with or without oxaliplatin (LV5FU2 vs. FOLFOX) for curatively-resected, node-positive esophageal squamous cell carcinoma

Background

Optimal perioperative treatment for resectable esophageal squamous cell carcinoma remains investigational. In this study, we evaluated the efficacy and safety of leucovorin and 5-fluorouracil (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX) combination chemotherapy given as adjuvant therapy for curatively-resected, node-positive esophageal squamous cell carcinoma.

Methods

Patients with pathological node-positive esophageal cancer after curative R0 resection were enrolled in a Fleming's single-stage phase II design. Patients were randomly assigned to receive LV5FU2 (leucovorin 200 mg/m² and 5-FU 400 mg/m² intravenously on day 1, followed by a 46-h infusion of 5-FU 2,400 mg/m²) or FOLFOX (oxaliplatin 85mg/m² as 2-hr infusion on day 1 plus LV5FU2). Patients received either LV5FU2 or FOLFOX biweekly up to 8cycles except disease progression or unacceptable toxicity. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), safety and quality of life assessments.

Results

Between Jan 2011 and Mar 2015, 66 patients were randomized (35 in LV5FU2 arm and 31 in FOLFOX arm). The median age of all patients was 60 years (range, 43-77) and both groups had similar pathologic characteristics in tumor, nodal status and location. About 70% of patients had stage II or III disease. Treatment completion rates were similarly high in both groups (P = 0.227). DFS rate at 12 month was 63% in LV5FU2 group versus 61% in FOLFOX group with hazard ratio (HR) of 1.3 (95% CI 0.68-2.52). After a median follow up of 27 months, the median DFS was 24.6 months (95% CI 4.5-44.7) in LV5FU2 arm and 15.6 months (95% CI 6.3-24.9) for FOLFOX arm (P = 0.423), respectively and median OS was not reached in both arms (P = 0.817). Grade 3 or higher neutropenia was more frequent in patients in the FOLFOX arm compared to with the LV5FU2 arm (19.3% vs 2.9%), but none had febrile neutropenia.

Conclusions

No evidence was found that the addition of oxaliplatin (FOLFOX) improves efficacy compared to LV5FU2 chemotherapy as adjuvant setting in esophageal cancer patients with lymph node-positive.

Clinical trial identification

ClinicalTrials.gov NCT01467921

Legal entity responsible for the study

Institutional review boards of Samsung Medical Center

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.