A Comparison of Multimodal Therapy and Surgery for Esophageal Adenocarcinoma

Abstract

Background Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. Methods Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. Results Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P Ͻ 0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses, as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P ϭ 0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P ϭ 0.01). Conclusions Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.

A Phase II Study with Lead-In Safety Cohort of 5-Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2-Positive Esophagogastric Adenocarcinomas

“…Twelve patients (median age 64 years; 67% male, 58% moderately differentiated, 83% esophageal, 100% HER2‐positive) received a median of 5.6 weeks of treatment (range: 1.1–8.4). Four patients underwent tumor resection and one of the four patients (25%) had a pCR, which was similar to the pCR rates of previously reported studies [1], [2], [3]. However, the number of patients evaluated in the present study was too low to make an accurate comparison with other studies.…”

“…Neoadjuvant chemoradiation therapy for patients with localized esophagogastric cancers has been the subject of much discussion and controversy, with conflicting results compared with surgery alone seen in previous randomized clinical trials [1], [2], [3]. Pathologic complete response (pCR) rates after neoadjuvant chemoradiation therapy are in the 25% range [1], [2], [3].…”

“…Pathologic complete response (pCR) rates after neoadjuvant chemoradiation therapy are in the 25% range [1], [2], [3]. …”

The accuracy of endoscopic ultrasound for restaging esophageal carcinoma after chemoradiation therapy

“…1,3,4 Several authors have investigated the beneficial role of neoadjuvant chemoradiation therapy (CRT) in patients with potentially resectable esophageal adenocarcinoma to improve long-term survival. 5,6 Local preoperative staging of esophageal carcinoma with EUS is important in selecting better candidates for surgery and in determining which patients have potentially resectable disease. Studies have continued to support the utility of EUS in the initial staging of esophageal carcinoma.…”

Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model

“…Subset analyses demonstrate that only true complete responders have a durable diseasefree and overall survival benefit. [26][27][28][29] The addition of gene therapy to currently employed modalities of chemotherapy, radiotherapy and surgery attempts to enhance the overall antitumor efficacy and increase the number of complete responders. It has been reported that MUC1 is expressed in as high as 43% of esophageal adenocarcinoma specimens and that a majority of these specimens were poorly differentiated advanced neoplasms.…”