OncoGel (ReGel/paclitaxel)--clinical applications for a novel paclitaxel delivery system.

Cancer treatment regimens often include multiple anticancer agents targeting different cellular mechanisms in delicate balance with associated toxicity. Drug delivery systems offer a unique tool in the treatment of cancer, and applications in the local treatment of cancer have demonstrated utility in providing sustained high local concentrations at the tumor site while minimizing systemic drug levels. Treatment options for local cancer therapy are focused on indications where targeted activity may result in improved patient outcomes such as increased local control and decreased metastatic potential. Targeted therapies may also enhance response to combination anticancer regimens. OncoGel, a controlled-release depot formulation of paclitaxel in ReGel, has been evaluated in numerous nonclinical studies. Results from these studies demonstrated OncoGel's ability to physically target paclitaxel to the tumor site with very little reaching the circulation, resulting in an acceptable safety profile with dose-limiting toxicities being local in nature. In addition, OncoGel demonstrated efficacy as a stand-alone treatment and synergistic activity in combination therapies. Clinical studies in superficially-palpable tumors and esophageal carcinoma confirmed local paclitaxel release from OncoGel in patients. OncoGel's ability to improve current treatment options for esophageal and brain cancers is being further evaluated.

Phase 2: a dose-escalation study of OncoGel (ReGel/paclitaxel), a controlled-release formulation of paclitaxel, as adjunctive local therapy to external-beam radiation in patients with inoperable esophageal cancer.

OncoGel, a novel injectable formulation of paclitaxel in a biocompatible biodegradable gel (ReGel), provides controlled release of paclitaxel at the injection site, resulting in high intralesional paclitaxel concentrations and continuous radiosensitization without attendant systemic toxicities. This dose-escalation study evaluated the toxicity, pharmacokinetics, and preliminary antitumor activity of OncoGel injected intralesionally in patients with inoperable esophageal cancer who were candidates for palliative external-beam radiotherapy (RT). Eleven patients with inoperable advanced esophageal cancer received a single administration of OncoGel into the primary tumor using conventional endoscopic techniques. Three cohorts received approximately one-third of the tumor volume with increasing paclitaxel concentrations to achieve 0.48, 1.0, and 2.0 mg paclitaxel/cm tumor volume. Subsequent to injection, RT was initiated (50.4 Gy in 1.8 Gy fractions). Pharmacokinetic sampling was performed. All patients completed the study. No dose-limiting toxicities were reported. Dysphagia improved and tumor size decreased in most patients. Biopsies were negative for carcinoma in 4 of 11 patients. Peak paclitaxel plasma concentrations were low (0.53-2.73 ng/ml) and directly related to the absolute amount of paclitaxel administered. Paclitaxel was detectable in plasma for 24 h in all patients and for 3 weeks in six patients. OncoGel given as an adjunct to RT was well tolerated in patients with inoperable esophageal cancer and provided prolonged paclitaxel release with minimal systemic exposure. OncoGel plus RT seemed to reduce tumor burden as evidenced by dysphagia improvement, tumor size reduction, and negative esophageal biopsies. The addition of OncoGel to combined modality therapy merits continued clinical development.