title: EUS-guided paclitaxel injection as an adjunctive therapy to systemic chemotherapy and concurrent external beam radiation before surgery for localized or locoregional esophageal cancer: a multicenter prospective randomized trial.
abstract: OBJECTIVE
  OncoGel (Protherics Salt Lake City, Inc, Salt Lake City, UT) is paclitaxel (PTX) formulated in a thermosensitive, biodegradable copolymer for focused cytotoxicity and radiosensitization. A phase 2a study suggested that EUS-guided PTX injection into esophageal tumors subsequently receiving radiotherapy was safe.
  
  
  METHODS
  In an international multicenter, prospective, randomized phase 2b study, patients with local or locoregional adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus/gastroesophageal junction and eligible for neoadjuvant chemoradiotherapy (CRT) before surgery were randomized to standard of care (SOC) plus EUS-guided PTX injection or SOC alone. PTX was injected in 0.5 to 1.0 mL aliquots throughout the tumor. Planned CRT as SOC was intravenous 5-fluorouracil for the first 4 days (weeks 1 and 5), intravenous cisplatin on the first day of each 5-fluorouracil course, and radiotherapy over 5.5 weeks. Patients were evaluated weekly during CRT and re-evaluated at 12 weeks for surgical eligibility and CT for change in overall tumor volume.
  
  
  RESULTS
  The analysis included 137 patients (97 males; mean age, 58 ± 9.1 years) randomized to PTX + SOC (n = 72) and SOC (n = 65) by using a modified intention-to-treat approach. Overall response by tumor volume between the PTX (12.5%) and the SOC group (20.0%; P = .24; odds ratio, 0.57; 95% confidence interval, 0.23-1.44) was similar. Pathologic complete response was higher in the SOC group (26.2% vs 12.5%; P = .046); however, 12-month survival (P = .412) and the overall frequency of 1 or more adverse events (P = .17) were similar between the 2 groups.
  
  
  CONCLUSIONS
  SOC + PTX is safe but does not improve overall survival or overall tumor response at the primary tumor site for patients with local or locoregional cancer of the esophagus/gastroesophageal junction. (Clinical trial registration number: NCT00573131.).
authors.affiliation: Gastroenterology, Indiana University Medical Center, Indianapolis, Indiana, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: DeWitt
authors.affiliation: Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: S Krishna
authors.initials: SK
authors.lastname: Murthy
authors.affiliation: Gastrointestinal Surgery, Meenakshi Mission Hospital and Research Centre, Madurai, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ardhanari
authors.affiliation: Gastroenterology, Endoscopy Center of Tyler Texas, Tyler, Texas, USA.
authors.forename: G Aaron
authors.initials: GA
authors.lastname: DuVall
authors.affiliation: Gastroenterology, Medical University of Lublin, Lublin, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wallner
authors.affiliation: Protherics Salt Lake City Inc, Salt Lake City, Utah, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Litka
authors.affiliation: Protherics Salt Lake City Inc, Salt Lake City, Utah, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Daugherty
authors.affiliation: Protherics Salt Lake City Inc, Salt Lake City, Utah, USA.
authors.forename: Kirk
authors.initials: K
authors.lastname: Fowers
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000556:secondary / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D019160:Endosonography; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015552:Injections, Intralesional; D057194:Intention to Treat Analysis; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011878:Radiotherapy; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate; D047368:Tumor Burden
chemical_list: D002945:Cisplatin; D005472:Fluorouracil