Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma

Inclusion Criteria:

• Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ) that is:

1. Stage IB (T1N1 only, T2N0 not eligible) - IIIC, i.e. T3 - T4 and/or nodepositive, according to American Joint Committee on Cancer (AJCC) 7th edition.

2. Considered operable following initial staging investigations (surgeon believesthat an R0 resection can be achieved) (GEJ tumours are defined as tumours thatarise in the cardia or at the GEJ that do not involve more than 2cm of thelower esophagus, i.e. Siewert Type II and Siewert Type III)

• Age >=18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Adequate organ function defined as follows:

1. Bone marrow: Haemoglobin >=90 g/L, Absolute neutrophil count (ANC) >=1.5 x 10⁹ /L, White blood cell count >=3 x 10⁹ /L, Platelet count >=100 x 10⁹ /L

2. Hepatic: Serum bilirubin <=1.5 x upper limit of normal (ULN), aspartateaminotransferase (AST) and/or alanine transaminase (ALT) <=3.0 x ULN

3. Renal: Serum creatinine <=0.150 mmol/L, Calculated creatinine clearance >=50mL/min

• Disease which can be radically treated with radiotherapy to 45 Gy with standardfractionation

• Any patient with a history of ischaemic heart disease and abnormal ECG, or who isover 60 years of age should have a pre-treatment evaluation of cardiac function witha multigated acquisition (MUGA) scan or echocardiogram. Patients will only beincluded if the left ventricular ejection fraction is >=50%.

• Written informed consent obtained before randomization

• Negative pregnancy test for women of childbearing potential within 7 days ofcommencing study treatment. Males and females of reproductive potential must agreeto practice adequate contraceptive measures.

Exclusion Criteria:

• Evidence of metastatic disease

• Prior chemotherapy or radiotherapy

• Patients with a past history of cancer in the 5 years before randomization exceptfor the following. Patients with squamous or basal cell carcinoma of the skin thathas been effectively treated, and patients with carcinoma in situ of the cervix thathas been treated by operation only are eligible, even if they were diagnosed andtreated within the 5 years before randomization.

• Patients with other significant underlying medical conditions that may be aggravatedby the study treatment or are not controlled

• Pregnant or lactating females or female patients of childbearing potential who havenot been surgically sterilized or are without adequate contraceptive measures

• Cardiac failure and other contraindications to epirubicin

• Patients with impaired gastrointestinal absorption for whatever reason

• Patients medically unfit for cisplatin chemotherapy due to one or more of thefollowing reasons:

1. Clinically significant sensorineural hearing impairment (audiometricabnormalities without corresponding clinical deafness will not be regarded as acontraindication to cisplatin)

2. Severe tinnitus

3. Renal impairment (GFR <=50ml/min)

4. Peripheral neuropathy >=grade 2

5. Inability to tolerate intravenous hydration e.g due to cardiac disease

6. Co-morbidities (based on clinical judgement by the investigator) that in theview of the investigator would preclude the safe administration of cisplatin.