study of the interest of pursuing or not the chemotherapy for patients with metastatic esophageal cancer

Conditions: Esophageal Cancer, Squamous Cell

Summary: 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

Eligibility criteria:
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