Neoadjuvant Epirubicin, Cisplatin and Capecitabine (ECX) Followed by Definitive Chemoradiation With/Without Surgery for Squamous Cell Carcinoma of the Oesophagus

Neoadjuvant Epirubicin, Cisplatin and Capecitabine (Xeloda) [ECX] Followed by Definitive Chemoradiation With or Without Surgery for Patients With Newly Diagnosed Localized Squamous Cell Carcinoma of the Oesophagus

This is a study to investigate the efficacy and safety of epirubicin, cisplatin and capecitabine (ECX) as neoadjuvant therapy prior to radical chemoradiotherapy using capecitabine and cisplatin as radio-sensitisers in patients with newly diagnosed localized squamous cell carcinoma of the oesophagus.

Inclusion Criteria:

• Age > 18 years.
• Histologically verified squamous cell carcinoma of the cervical or thoracic oesophagus
• American Joint Committee on Cancer (AJCC) Stage I-III (T1-3 N0-1 M0) (33), as assessed by spiral or multi-slice computed tomography (CT) and endoscopic ultrasound, where radical chemoradiation would be considered with curative intent.
• No previous chemotherapy, radiotherapy or other investigational drug treatment for this indication.
• World Health Organization (WHO) performance status 0,1 or 2.
• Adequate bone marrow function with platelets > 100 x 10^9/l; white blood cells (WBC) > 3 x 10^9/l; neutrophils > 1.5 x 10^9/l at the time of study entry.
• Serum bilirubin < 35 micromol/l.
• Serum creatinine < 180 micromol/l and measured creatinine clearance over 60 ml/min.
• No concurrent uncontrolled medical condition.
• No previous malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix in the last 10 years.
• Life expectancy > 3 months.
• Adequate contraceptive precautions if relevant.
• Informed written consent.

Exclusion Criteria:

• The presence of locally advanced or metastatic disease precluding curative chemoradiation (T4 or Stage IV or M1a-b) or disease not encompassable in a radical radiotherapy field.
• Total dysphagia (O'Rourke's swallowing function scoring system 5) precluding swallowing of capecitabine even when crushed.
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Intracerebral metastases or meningeal carcinomatosis.
• New York Heart Association classification Grade III or IV.
• Uncontrolled angina pectoris.
• Pregnancy or breast feeding.
• Impaired renal function with measured creatinine clearance less than 60 ml/min.
• Previous investigational study drug
• Known malabsorption syndromes
• Patients with a known hypersensitivity to fluorouracil (5-FU) or with a dihydropyrimidine dehydrogenase (DPD) deficiency
• Hearing loss