This decision was taken on June 20 2022 due to low recruitment over the past 4 years.

Phase II study, randomized, open-label, multicentric, willing to establish the benefit of pursuing chemotherapy beyond 6 weeks for non progressive patients. The study will proceed in two successive phases :

• non randomized phase in which all patients will undergo chemotherapy
• second phase in which only non progressive patients are going to be randomized ("discontinuation design"). Patients that will show progression in their disease during the first 6 weeks will be released of the study

Initial phase: this part of the trial consist of 3 cycles of LV5FU2 (Bolus 5-FU 400mg/m² - 5-FU continuously during 46h: 3000 mg/m², calcium levofolinate 200 mg/m²) - paclitaxel (100 mg/m² at day 1) every 14 days. After 6 weeks,the phase will end with a check-up (clinical exam, tumor evaluation and biological test). Then, if the disease is non-progressive, the patient will proceed to the randomized phase.

Randomized phase:

• Arm A : pursuit of chemotherapy and best supportive care
• Arm B : interruption of chemotherapy and best supportive care

Inclusion Criteria:

• Patients suffering from squamous-cell type esophageal cancer histologically proved
• Metastatic disease measurable according to RECIST criteria. Patients with metachronous metastasis and who have been treated with surgery (+/- radio chemotherapy concurrent or adjuvant chemotherapy) or exclusive radio chemotherapy, are eligible
• Patients who show progress under chemotherapy that associates a fluoropyrimidine with a platinum salt
• Man or woman over 18 years old
• ECOG performance status ≤ 2
• Adequate haematological, renal and hepatic functions : PNN ≥ 1500/ mm3; platelets ≥ 100 000/ mm3; Haemoglobin ≥ 9.0 g/dL; ALT and AST ≤ 2.5 ULN (≤ 5.0 in case of liver metastases); Total bilirubin ≤ 1.5 X ULN; Serum creatinine ≤ 1.5 ULN
• Efficient contraceptive method for both gender (if applicable), during the whole treatment period and the 6 months following the last treatment administration
• Affiliation to the National Social Security System
• With informed and signed consent

Inclusion Criteria for randomization:

• ECOG performance status ≤ 2
• Able to pursuit the LV5FU2-paclitaxel chemotherapy
• Non-progressive disease after the initial phase (first tumor exam at week 6)

Exclusion Criteria:

• Patients who received more than one line of chemotherapy for a metastatic disease
• Presence of other evolutive tumors
• Cerebral metastasis or other known brain tumors
• Severe liver failure
• Pernicious anemia or other anemia due to vitamin B12 defficiency
• Hypersensibility to an active substance or any other excipients of experimental drugs
• Every unstable chronicle diseases that can affect patient confidence or security
• Clinically significant active cardiac disease or myocardial infarction in the 6 previous months
• Patients with a known dihydropyrimidine dehydrogenase (DPD) deficiency
• Concomitant treatment with : sorivudin or analogs; prophylactic phenytoin
• Live attenuated vaccine within the 3 previous months
• Pregnant or breastfeeding women
• Unable to comply with the medical monitoring for geographic, social or mental issues
• Patient Under guardianship or tutorship