Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

Abstract

Background/aim: Prognoses of patients receiving radio-chemotherapy with 5-fluorouracil (5-FU) and cisplatin for unresectable esophageal cancer may be improved with the addition of cetuximab. This phase I study aimed to define the maximum tolerated dose of 5-FU when combined with cisplatin, cetuximab and radiotherapy.

Patients and methods: Treatment included 59.4 Gy of radiotherapy concurrently with two courses of cisplatin (20 mg/m², d1-4) and 5-FU (dose level 0: 500 mg/m², dose level 1: 750 mg/m², d1-4; dose level 2: 1,000 mg/m², d1-4), followed by two courses of chemotherapy. Cetuximab was given for 14 weeks (400 mg/m² loading dose followed by 250 mg/m² weekly).

Results: At dose level 1 (n=3) and 2 (n=3), no patient experienced a dose-limiting toxicity. Minor treatment modifications were due to organization or request by physicians/patients. At dose level 2, only five grade 3 adverse events occurred.

Conclusion: Dose level 2 appears safe and is used in a subsequent randomized phase II study.

Keywords: Locally advanced esophageal cancer; cetuximab; definitive radio-chemotherapy; dose-limiting toxicities; phase I study.