A multicenter randomized phase II (rPII)/III study comparing concurrent chemoradiotherapy (CRT) with low-dose cisplatin plus continuous infusion of 5-fluorouracil (LDPF) and standard-dose PF (SDPF) for locally advanced unresectable squamous cell carcinoma of the thoracic esophagus (JCOG0303).

Abstract

4053 Background: Cisplatin-based CRT is one of the standard treatments for locally advanced unresectable esophageal carcinomas. Although both cisplatin and 5-FU are known to enhance the efficacy of radiotherapy, the optimal chemotherapy regimen has not been established. Thus, we evaluated CRT with LDPF on effectiveness and adverse events for locally advanced unresectable esophageal carcinomas in a randomized study to determine if it is an acceptable alternative to SDPF. Methods: Eligibility criteria included histologically proven squamous cell, adenosquamous, or basaloid carcinoma; tumor located in thoracic esophagus; and definite T4 and/or unresectable regional lymph node metastasis. In arm A, two courses of standard chemotherapy of cisplatin (70 mg/m2, div day1, 29) plus 5-FU (700 mg/ m2, ci day1-4, 29-32) were given with external beam radiation (EBRT) in 30 daily fractions, 5 d/week to a total dose of 60 Gy. In arm B, low dose daily cisplatin (4 mg/ m2, div) plus 5-FU (200 mg/ m2, ci) was administered on the same days that EBRT was given. The primary endpoint was overall survival (OS). The rPII study was designed to evaluate the efficacy of LDPF to decide whether it warranted a phase III trial. Results: Between Apr. 2004 and Jun. 2009, 135 pts (Arm A/B; 67/68) from 40 institutions were randomized. Tumor depth (T1-3/T4) was 18/49 in arm A and 13/55 in arm B. The median follow-up time for all eligible pts was 9.9 mos. Toxicities were almost equivalent in both arms; however LDPF necessitated long hospitalization. Moreover, the OS of pts of LDPF group was slightly inferior to that of those treated with SDPF (hazard ratio, 1.048, 95%CI, 0.782-1.045; median OS (A/B), 13.0/13.6 mos.; 3-year OS (A/B), 30/26%). Because of the inferior efficacy of LDPF, the Data and Safety Monitoring Committee of the JCOG recommended the termination of the study at the end of rPII. Conclusions: CRT with LDPF is not recommended for pts with locally advanced unresectable esophageal cancer. No significant financial relationships to disclose.