Title
Radiochemotherapy With and Without Dose Escalation in Patients Presenting Locally Advanced or Inoperable Carcinoma of the Oesophagus
Prodige 26: Radiochemotherapy With and Without Dose Escalation in Patients Presenting Locally Advanced or Inoperable Carcinoma of the Oesophagus
Phase
Phase 2/Phase 3Lead Sponsor
Centre Georges Francois LeclercStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Esophageal CancerIntervention/Treatment
fluorouracil leucovorin oxaliplatin ...Study Participants
196Exclusive concomitant radiochemotherapy (RCT) at a dose of 50 Gy delivered over 5 weeks, according to the RTOG 85-01 protocol, has led to improved 5-year survival in 25% of patients, whereas no patients survived for 5 years using radiotherapy alone for patients with esophageal cancer. Surgery, even when combined with preoperative RCT, also gives disappointing results for locally advanced tumors, which casts serious doubts on the usefulness of preoperative radiotherapy. By varying the fractionation schedule, the length of treatment or the radiotherapy volumes, it has become possible to obtain levels of loco-regional relapse of around 35 to 45%. After reviewing the results for loco-regional relapse according to the dose of radiation and the recommended radiotherapy volumes, we aimed to investigate why increasing the dose of radiation has no impact in esophageal cancers. Although INT-0123 phase III trial showed no benefit of dose escalation in esophageal cancer, some issues remain unclear as most of the patients who died in the experimental arm were treated above 50Gy. Moreover, only the tumor was treated up to 64Gy while involved nodes were not considered for dose escalation in this trial. In the RTOG 85-01phase III trial, an elective nodal irradiation from subclavicular fossa up to the esophagogastric junction was performed with a 2D technique, delivering 30Gy which could be considered as not appropriate.
In this randomized phase II/III trial, we aim to test an exclusive concomitant chemoradiotherapy for patients with non resectable esophageal cancer with a dose escalation up to 66Gy on the primary tumor as well as the involved nodes using a 3D conformal technique combined with a 40 Gy elective nodal irradiation on lymph node stations (as defined by the RTOG) with a risk of microscopic involvement ≥ 20%.
40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)
Boost 10 Gy in 5 fr, PTV = +1cm.
Boost 26 Gy in 13 fr, PTV = +1cm.
6 treatments with 4 courses concomitant to radiotherapy (D1, D15, D29, D43) arm B or 3 courses concomitant to radiotherapy (D1, D15, D29) arm A.
Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph nodes: Radiotherapy 40 Gy, in 20 fractions / 4 weeks: PTV (1cm in every direction) Boost 10 Gy in 5 fr: PTV = +1cm. Chemotherapy FOLFOX 4: 6 treatments in 3 courses concomitant to the radiotherapy (D1, D15, D29)
Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph nodes: 40 Gy in 20 fractions / 4 weeks, PTV (1cm in every direction) Boost 26 Gy in 13 fr: PTV = +1cm. Chemotherapy: FOLFOX 4: 6 treatments with 4 courses concomitant to radiotherapy (D1, D15, D29, D43).
Inclusion Criteria: Age> or = 18 and < 75 ans WHO Status 0, 1 and 2 Enteral or parenteral feeding (> or = 1500 KCal) planned before the start of treatment Histologically proven carcinoma of the oesophagus Histological Types: adenocarcinomas and epidermoid carcinomas T3, N0-N1-N2-N3, M0 (TNM version 7) T1-T2, N0-N1-N2-N3, M0 with a contra-indication for surgery (TNM version 7) Absence of trachea-oesophageal fistula Written informed consent Woman under appropriate contraception Patient able to understand and complete, with help if necessary, a quality of life questionnaire Exclusion Criteria: Evolutive heart failure or myocardial necrosis for less than 6 months Myocardial infarction of more than 6 months with ischemic sequelae on myocardial scintigraphy. Patient cannot absorb at least 1500kcal/j before and/or during treatment Left heart failure. Stage II to IV arteriopathy in the Leriche and Fontaine classification Creatinine > or = 1.25x N PNN < 1,5.109 /l Platelets < 100. 109 /l Albumin < 30g/l TP < 60% without anticoagulant VEMS < 1l History of cancer (except baso-cellular cutaneous epithelioma or in situ epithelioma of the cervix) that has relapsed in the 5 years preceding recruitment for the trial Patient already enrolled in another therapeutic trial with an experimental molecule Women who are pregnant or likely to be so, or who are breastfeeding People who are in custody or under guardianship Impossibility to adhere to the medical follow up for the trial for geographical,social or psychiatric reasons. Presence of a history of radiotherapy to the chest or upper abdomen for another tumour Peripheral neuropathy > or = grade 1 (CTC v3.0)
