A randomized phase 3 trial comparing paclitaxel plus 5-fluorouracil versus cisplatin plus 5-fluorouracil in Chemoradiotherapy for locally advanced esophageal carcinoma-the ESO-shanghai 1 trial protocol.

BACKGROUND: Concurrent chemoradiotherapy is a standard modality for locally advanced esophageal squamous cell carcinoma (ESCC) patients. Cisplatin combined with 5-fluorouracil continuous infusion (PF) remains the standard concurrent chemotherapy regimen. However, radiotherapy concurrent with PF showed a high incidence of severe side effects. Paclitaxel showed a promising radiosensitivity enhancement in the treatment of esophageal carcinoma in both vitro and vivo studies. The ESO-Shanghai 1 trial examines the hypothesis that paclitaxel plus 5-fluorouracil (TF) concurrent with radiotherapy has better overall survival and lower toxicity for patients with local advanced ESCC.

METHOD: Four hundred thirty-six ESCC patients presenting with stage IIa to IVa will be enrolled in a prospective multicenter randomized phase 3 study. Patients will be randomized to either concurrent chemoradiotherapy with PF (cisplatin 25 mg/m2 /d, d1-3, plus 5-fluorouracil 1800 mg/m2 , continuous infusion for 72 h) once every 4 weeks for 2 cycles followed by consolidation chemotherapy for 2 cycles or concurrent chemoradiotherapy with weekly TF (5-fluorouracil 300 mg/m2 , continuous infusion for 96 h plus paclitaxel 50 mg/m2 , d1) for 5 weeks followed by consolidation chemotherapy (5-fluorouracil 1800 mg/m2 , continuous infusion for 72 h, plus paclitaxel 175 mg/m2 d1) once every 4 weeks for 2 cycles. The radiotherapy dose is 61.2 Gy delivered in 34 fractions to the primary tumor including lymph nodes. The primary end-point is the 3-yr overall survival analyzed by intention to treat. The secondary endpoints are disease progression-free survival, local progression-free survival, and number and grade of participants with adverse events.

DISCUSSION: The aim of this phase 3 study is to determine whether the TF regimen could replace the standard PF regimen for inoperable ESCC patients. An overall survival benefit of 12% at 3 years should be expected in the TF group to achieve this goal.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01591135 . Registered 18 April 2012.