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

Gastrointestinal Endoscopy, 04/30/2012

Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 × 1010 particle units (PU) and is associated with long survival. This regimen warrants additional studies.

Methods

  • Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 × 108 to 4 × 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.
  • 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 × 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.

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