Feasibility Study of Neoadjuvant Chemoradiotherapy with Cisplatin Plus 5-Fluorouracil for Clinical Stage II/III Esophageal Squamous Cell Carcinoma

ABSTRACT Background Based on the JCOG 9907 trial results, neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered a standard treatment of stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory and neoadjuvant chemoradiotherapy (NeoCRT) may improve the outcome of stage II/III ESCC patients. We conducted a feasibility study of NeoCRT with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC. Methods Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, PS 0-1, and age 20–75 years. Chemotherapy consisted of two courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to a total 41.4 Gy in 23 fractions for primary tumor, metastatic lymph nodes (LNs) and regional LNs. Esophagectomy with extensive lymphadenectomy (≥D2) was carried out 42–56 days after NeoCRT. The primary end point was the completion rate of NeoCRT and R0 resection. Results Thirty-three patients were enrolled, including 2 ineligibles. In 31 eligible patients, the median age was 63 years (range, 40–73); PS0/1: 19/12; cStage IIA/IIB/III: 2/10/19. The completion rate of protocol treatment was 93.5% (29/31). During CRT, the most common grade 3 or 4 toxic effects were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%), hyponatremia (16%). One treatment-related death was observed. The incidence of operative morbidity was similar to that in previous studies but incidence of anastomotic leakage was observed more frequently (27%). According to RECIST, the overall response rate was 78% (14/18) after CRT. Pathological complete response was achieved in 42% (13/31). Conclusions NeoCRT was tolerable and active. The randomized, controlled trial compared with neoadjuvant chemotherapy is needed and we plan it.