Neoadjuvant Radiochemotherapy in Local Advanced Squamous Cell Carcinoma of the Esophagus With Weekly Cetuximab Plus Oxaliplatin Plus Continuous IV. 5-FU and Conventional Fractionated External Multi-Field Irradiation up to 45 Gray. A Phase I/II Study
- Determine the maximum tolerated dose of oxaliplatin and fluorouracil when administered
with cetuximab and radiotherapy in patients with stage II or III squamous cell
carcinoma of the esophagus. (Phase I)
- Determine the response rate in patients treated with this regimen. (Phase II)
- Determine the toxicity of this regimen in these patients.
- Determine the postoperative complication rate and lethality in patients treated with
- Determine the R0 resection rate in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Determine the event-free survival of patients treated with this regimen.
- Determine the metabolic response rate in patients treated with this regimen.
OUTLINE: This is a phase I, dose-escalation study of oxaliplatin and fluorouracil followed
by an open-label, phase II study.
- Phase I: Patients receive cetuximab IV over 60-90 minutes on days -15, -8, 1, 8, 15,
22, and 29; oxaliplatin IV over 120 minutes on days 1, 8, 22, and 29; and fluorouracil
IV continuously on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients undergo
radiotherapy on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients then undergo radical
esophagectomy 29-42 days after the completion of chemoradiotherapy.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive oxaliplatin and fluorouracil as in phase I at the MTD
determined in phase I. Patients also receive cetuximab and undergo radiotherapy and
radical esophagectomy as in phase I.
After completion of study therapy, patients are followed every 3 months for 2 years and then
every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of oxaliplatin and fluorouracil (Phase I)
Florian Lordick, MD
Technische Universität München