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Phase I evaluation of TNFerade biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer.

Abstract：

BACKGROUND:Neoadjuvant chemoradiotherapy followed by surgery is the primary treatment option for patients with locally advanced esophageal cancer. This multicenter phase I trial examined intratumoral injection of TNFerade biologic, an adenoviral vector that expresses the human tumor necrosis factor-α gene, with chemoradiotherapy in locally advanced esophageal cancer. OBJECTIVES: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. DESIGN/INTERVENTION:Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 × 10(8) to 4 × 10(11) particle units (PU), were given in combination with cisplatin 75 mg/m(2) and intravenous 5-fluorouracil 1000 mg/m(2)/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. SETTING:U.S. multicenter study. PATIENTS:Patients with stage II and III esophageal cancer were enrolled. MAIN OUTCOME MEASUREMENTS:Primary outcome measures were safety, feasibility, tolerability, and rate of pCR. Secondary outcome measures were overall survival (OS) and disease-free survival. RESULTS: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 × 10(11) 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. LIMITATIONS:We included primarily adenocarcinoma. CONCLUSIONS:Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 × 10(10) PU and is associated with long survival. This regimen warrants additional studies.

journal_name

Gastrointest Endosc

journal_title

Gastrointestinal endoscopy

authors

Chang KJ,Reid T,Senzer N,Swisher S,Pinto H,Hanna N,Chak A,Soetikno R

doi

10.1016/j.gie.2012.01.042

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

1139-46.e2

issue

eissn

0016-5107

issn

1097-6779

pii

S0016-5107(12)00101-0

journal_volume

pub_type

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Phase I evaluation of TNFerade biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer.