Blood-borne Assessment of Stromal Activation in Esophageal Adenocarcinoma to Guide Tocilizumab Therapy

Inclusion Criteria:

* Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction.
* Surgical resectable (\<T4b, N0 or N+, M0), as determined by Endoscopic UltraSound (EUS) and/or CT scan of neck, thorax and abdomen. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled.
* T1N+ tumors are eligible.
* Tumor length longitudinal ≤ 10 cm; if larger than 10 cm, inclusion should be discussed with the principal investigator.
* If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction.
* Age ≥ 18.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate hematological, renal and hepatic functions defined as:

  * neutrophiles ≥ 1.5 x 109/L
  * platelets ≥ 100 x 109/L
  * hemoglobin ≥ 5.6 mmol
  * total bilirubin ≤ 1.5 x upper normal limit
  * creatinine clearance (Cockroft) \> 60 ml/min
* Written, voluntary informed consent
* Patients must be accessible to follow up and management in the treatment center

Exclusion Criteria:

* Past (within 5 years) or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer, not including superficial and adequately treated skin and cervical malignancies.
* Previous chemotherapy, radiotherapy and/or treatment with Interleukin-6 (IL6) receptor blockers for esophageal cancer
* Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor.
* Previous chemotherapy and/or treatment with targeted agents and/or IL6 receptor blockers for other forms of cancer within the last six months.
* Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
* T1N0 tumors or in situ carcinoma.
* Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.
* Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
* Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.
* Pulmonary fibrosis and/or severely impaired lung function precluding major surgery.
* Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.
* Dementia or altered mental status that would prohibit the understanding and giving of informed consent
* Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding.
* Requires systemic treatment with IL6 receptor blockers or IL-6 antagonists, Tumor Necrosis Factor (TNF)-alpha blockers or other biologicals within the last six months before the first dose of trial treatment.
* Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
* Has an active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment.
* Has a total cholesterol \> 6.5 mmol/L despite adequate treatment with lipid-lowering agents.
* Has evidence of (latent) tuberculosis infection in patient history.
* Receiving a live or live weakened vaccine during treatment with tocilizumab
* Has evidence of acute or chronic infection with hepatitis B
* Patients with prior allogeneic stem cell or solid organ transplantation.
* Pre-existing motor or sensory neurotoxicity greater than World Health Organization (WHO) grade 1.
* Known allergy for tocilizumab or one of its excipients (sucrose, polysorbate 80, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dehydrate)