WASHINGTONPaclitaxel injected directly into esophageal tumors in conjunction with radiotherapy (RT) proved safe and technically feasible in a small phase IIa, dose-escalation trial reported at Digestive Disease Week 2007 (abstract M1934). "Tumor volume reduction, dysphagia improvement, and negative biopsies suggest this may be an effective therapy," concluded the authors, led by Kirk Fowers, PhD, a team leader in West Valley City, Utah, for London-based Protherics, PLC.
The investigational paclitaxel(Drug information on paclitaxel) formulation, known as OncoGel, is a low-viscosity, thermosensitive polymer that forms a gel at body temperature with controlled release of the drug over 6 weeks. Local administration is designed to provide both direct cytotoxicity and continuous radiosensitization without the adverse effects associated with systemic paclitaxel.
The trial enrolled 11 patients with inoperable adenocarcinoma or squamous-cell esophageal tumors and grade 3-4 dysphagia. OncoGel was injected directly into the primary tumor and accessible involved lymph nodes with endoscopic ultrasound guidance at escalating doses of 0.48, 1.0, and 2.0 mg of paclitaxel per cm3 of tumor volume. The patients then received external beam radiotherapy, 50.4 Gy, over 5.5 weeks.
No local or systemic dose-limiting toxicities were observed, and there were no serious OncoGel-related adverse events. Peak plasma concentrations of paclitaxel were 70 to 7,000 times lower than those reported with systemic therapy. While the drug remained localized for the most part, low levels were found in plasma in some patients for extended periods, supporting the notion of sustained release.
Tumor volume shrank in eight patients after 11 weeks. Dysphagia improved in nine patients. Four had negative biopsies following therapy, and one patient was able to undergo a successful esophagectomy with negative margins.
A randomized phase IIb study is planned to begin later this year, comparing OncoGel plus systemic chemotherapy and radiation to chemotherapy and radiation alone. The company also has launched a phase I/II trial of OncoGel as an adjuvant therapy postresection in recurrent glioblastoma multiforme.