To assess pathologic complete response (pCR), time to disease progression, progression-free survival, survival, and safety and tolerance in patients treated with preoperative chemoradiation combined with endoscopy or EUS-guided intratumoral injection of TNFerade biologic.
Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 ¡Á 108 to 4 ¡Á 1011 particle units (PU), were given in combination with cisplatin 75 mg/m2 and intravenous 5-fluorouracil 1000 mg/m2/d for 96 hours on days 1 and 29, and concurrent radiation therapy to 45 Gy. Surgery was performed 9 to 15 weeks after treatment.
U.S. multicenter study.
Patients with stage II and III esophageal cancer were enrolled.
Primary outcome measures were safety, feasibility, tolerability, and rate of pCR. Secondary outcome measures were overall survival (OS) and disease-free survival.
Twenty-four patients with a median age of 61 years were enrolled; 88 % of the patients were men, 21 % were stage II, and 79 % were stage III. Six (29 % ) had a pCR, observed among 21 patients (20 who underwent esophagectomy and 1 at autopsy). Dose-limiting toxicities were not observed. The most frequent potentially related adverse events were fatigue (54 % ), fever (38 % ), nausea (29 % ), vomiting (21 % ), esophagitis (21 % ), and chills (21 % ). At the top dose of 4 ¡Á 1011 PU, thromboembolic events developed in 5 of 8 patients. The median OS was 47.8 months. The 3- and 5-year OS rates and disease-free survival rates were 54 % and 41 % and 38 % and 38 % , respectively.
We included primarily adenocarcinoma.
Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 ¡Á 1010 PU and is associated with long survival. This regimen warrants additional studies. (Clinical trial registration number: .)