Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oesophagogastric Cancer

This is a combined eligibility criteria for both bevacizumab comparison and the lapatinib feasibility study. Please note the bevacizumab comparison closed to recruitment on 28th March 2014.

DISEASE CHARACTERISTICS:

* Histologically confirmed gastric or type I, II or III gastroesophageal junction adenocarcinoma or lower oesophageal

Gastric and Type III junctional tumours should be Stage Ib (T1 N1, T2a/b N0), II, III or stage IV (T4 N1 or N2) with no evidence of distant metastases (M0)

Lower oesophageal and Type I and II junctional tumours should be Stage II to Stage IVa (T1 N1, T2 N1, T3 N0-1, but not T2N0). T4 (N0 or N1) tumours are also eligible providing that they involve only the crura OR invade only the mediastinal pleura. Patients with nodal disease affecting the origin of the left gastric and splenic artery or coeliac axis (staged as M1a) are also eligible.

* Resectable disease
* Previously untreated disease

PATIENT CHARACTERISTICS:

* WHO performance status 0 or 1
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL (can be post transfusion)
* WBC ≥ 3,000/mm\^3
* Glomerular filtration rate ≥ 60 mL/min
* Proteinuria ≤ 1 g by 24-hour urine collection
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT and AST ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 3 times ULN (in the absence of liver metastases)
* INR ≤ 1.5
* PTT ≤ 1.5 times ULN
* FEV\_1 ≥ 1.5 L
* Cardiac ejection fraction ≥ 50% by MUGA scan or echocardiogram
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Must be fit enough to receive protocol treatment
* No other malignancies within the past 5 years except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
* No prior or concurrent significant medical conditions, including any of the following:

  * Cerebrovascular disease (including transient ischemic attack and stroke) within the past year
  * Cardiovascular disease, including the following:

    * Myocardial infarction within the past year
    * Uncontrolled hypertension while receiving chronic medication
    * Unstable angina
    * New York Heart Association class II-IV congestive heart failure
    * Serious cardiac arrhythmia requiring medication
  * Major trauma within the past 28 days
  * Serious nonhealing wound, ulcer, or bone fracture
  * Evidence of bleeding diathesis or coagulopathy
  * Recent history of any active gastrointestinal inflammatory condition (e.g., peptic ulcer disease, diverticulitis, or inflammatory bowel disease)

    * If patients have a known diagnosis of any of the above, evidence of disease control is required by negative endoscopy within the past 28 days
* No severe tinnitus
* No lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication
* No known peripheral neuropathy ≥ 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
* No known dihydropyrimidine dehydrogenase deficiency
* No history of interstitial lung disease or radiological evidence of lung fibrosis
* No known allergy to any of the following:

  * Chinese hamster ovary cell proteins
  * Other recombinant human or humanized antibodies
  * Any excipients of bevacizumab formulation or platinum compounds
  * Any other components of the study drugs

Due to an increase in perforations associated with self-expandable metal stents in patients with colorectal cancer receiving bevacizumab, patients with an oesophageal or gastric stent (metal or biodegradable) in situ are ineligible for the study.

PRIOR CONCURRENT THERAPY:

* No prior anthracycline
* More than 28 days since prior major surgery or open biopsy
* More than 10 days since prior thrombolytic therapy
* No concurrent thrombolytic therapy
* No concurrent dipyridamole
* No concurrent capecitabine or sorivudine (or sorivudine analogues \[e.g., brivudine\])
* No chronic, daily high-dose acetylsalicylic acid (\> 325 mg/day) or nonsteroidal anti-inflammatory drugs
* No chronic corticosteroids (≥ 10 mg/day methylprednisolone equivalent)

  * Inhaled steroids allowed
* No other concurrent cytotoxic agents
* No other concurrent investigational drugs
* No concurrent radiotherapy
* Low molecular weight heparin allowed
* More than 7 days since prior CYP3A4 inhibitor therapy
* More than 14 days since prior CYP3A4 inducer therapy
* More than 6 months since prior amiodarone therapy
* More than 14 days since prior St John's Wort, modafinil, ginkgo biloba, kava, grape seed, valerian, ginseng, echinacea and evening primrose oil