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

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. 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. 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. 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.).