Neoadjuvant Chemotherapy Versus Radiochemotherapy for Cancer of the Esophagus or Cardia

Study Overview
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Brief Summary
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The purpose of this randomized study is to clarify if neoadjuvant radiochemotherapy gives a higher degree of complete histological response than neoadjuvant chemotherapy before surgery in patients undergoing treatment for cancer of the esophagus or cardia.

Official Title
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Adjuvant Treatment of Cancer of the Esophagus or Cardia Before Resection With Curative Intent. Comparative Study Between Chemotherapy and Radiochemotherapy

Conditions
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Carcinoma, Squamous Cell, Adenocarcinoma of the Esophagus and Gastric Cardia

Intervention / Treatment
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* Drug: Chemotherapy
* Radiation: Radiochemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified squamos cell carcinoma, adenocarcinoma of the esopohagus or gastric cardia (type II) Tumor located in cervical oesophagus, not requiring laryngo-esophagectomy. Patients with performance status 0-1 axxording to WHO scale and with resectable tumours, as assessed at the prerandomisation evaluation Adequate haemotological function, defined as having WBC > 3 x 10(9)/litre and platelets > 100 x 10 (9)/litre. Adequate renal function defined as having normal serum creatinine level and/or calculated glomerular filtration rate > 60 ml/min. Tumour stage: T1Ni, T2N0, T2N1, T3N0, T3N1, M1a Exclusion Criteria: Pregnancy and/or lactation. Women of childbearing ages can be included and provided that adequate contraceptive methods are used Patients with diabetes complications (e.g. rethinopathy, neuropathy) as well as patients with uncontrolled cardiac disease or myocard infarction within 12 months are considered unsuitable for chemoradiotherapy. Concomitant malignancy (< 5 years since diagnosis) that can interfere the interpretation of study results, ongoing antitumoral treatment. Patients being unable tom comply with the protocol Tumor stage T1 N0, T4 NX or TXNXM1b

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiochemotherapy<br>Arm I: Radiochemotherapy + Surgery | Drug: Chemotherapy<br>* Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.<br>* Other names: Suffering moderate/severe hearing impairment and/or tinnitus cisplatin can be replaced. If adenocarcinoma oxaliplatin.If squamos cell carcinoma carboplatin.;Radiation: Radiochemotherapy<br>* Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.<br>* Other names: Suffering moderate/severe hearing impairment and/or tinnitus cisplatin can be replaced. If adenocarcinoma oxaliplatin.If squamos cell carcinoma carboplatin.;|
| Active Comparator: Chemotherapy<br>Arm II: Chemotherapy + surgery | Drug: Chemotherapy<br>* Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.<br>* Other names: Suffering moderate/severe hearing impairment and/or tinnitus cisplatin can be replaced. If adenocarcinoma oxaliplatin.If squamos cell carcinoma carboplatin.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia. | Chireac tumour regression grade | Therapy followed in 14-16 weeks before surgery. After surgery the patients will be followed until 60 weeks after completed therapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Respective Neoadjuvant Therapies. | Safety profile of carrying out radical surgery after respective neoadjuvant therapy. | Five years follow up | 
| HRQOL and Swallowing Function | The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease specific questionnaires (QLQ-OES24/OG25). All items included in the questionnaires are analysed and also separate analysis of dysphagia questionnaires for oesophageal cancer were used, both clinically and psychometrically validated. All questions have four response alternatives (1, not at all; 2:a little, 3: quite a bit, 4: very much), except global scales which comprise seven response alternatives from poor to excellent. Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 according to the EORTC scoring manual. A higher score indicates either more symotoms or better function, depending on the question. | Entry study up to Five years follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Histologically confirmed squamos cell carcinoma or adenocarcinoma of the esophagus and gastric cardia.Suitable for surgery.