From Bench to Bedside—An Example of an In Situ Hydrogel in In Vivo Applications - In-Situ Gelling Polymers: For Biomedical Applications - page 218

which euthanasia was performed in 14 days showed localized fibrotic tissue
changes and a decrease in inflammation.
Another study reported that the concentration of paclitaxel varied with the dis-
tance, with the high concentrations in the areas with the depot and low concentra-
tions areas 10-30 mm from the injection site [ 11 ]. The study used a similar EUS
guided injection of Oncogel™ and reported that the viscosity of the gel presented
difficulties which could be overcome by using a threaded syringe and pressure
tubing between the syringe and the EUS needle to increase the pressure. Though,
the absence of pancreatitis, sclerotic or neurotic tissue formation indicates a good
pancreatic tissue tolerability, further investigation is required to understand the
possibility of long-term complications such as bone marrow suppression, neuropa-
thy, cardiotoxicity.
3.3 Human-Clinical Trials
Pre-clinical studies of Oncogel™ established its cytotoxic potency and reported
it to be localized within the injection site, thereby attenuating the systemic toxici-
ties. As the research progressed beyond animal model studies, phase one clinical
studies were designed to evaluate the efficacy of Oncogel™ when administered
intralesionally to superficially accessible solid tumor lesions in patients who had
not undergone any other curative therapy [ 20 ]. The blood chemistry and the hema-
tology data was collected for 9 weeks following Oncogel™ injection. The tumor
response was gauged from 3D images obtained from CT scan, ultrasound and
MRI whereas caliper was used to obtain 2D measurements [ 5 ]. The main objec-
tive of this study was to identify the maximum tolerated dose (MTD) by observ-
ing the dose limiting toxicity (DLT) at various concentrations of Oncogel™. 16
patients receiving 0.06-2.0 mg paclitaxel/cm 3 tumor volume were under obser-
vation. Though Oncogel™ placement into the tumor was well tolerated at doses
up to 2.0 mg paclitaxel/cm 3 tumor volume, 8 patients were observed with adverse
local response to Oncogel™ administration such as injection site pain, muscle
spasms and erythema. However, even at the highest dose of Oncogel™, no DLTs
were reported, confirming the non-clinical studies data about the localization of
the Oncogel™ depot.
Efficacy analysis was also performed on the patients according to the modified
WHO criteria by comparing the change from baseline of the tumor volume every
4 weeks. 6 patients were reported to have a stable disease, and 8 patients were
classified as having progressive disease. However, the significance of these results
remains questionable due to the small sample size and varied tumor types (breast,
lymphoma, malignant melanoma, etc.). On the other hand, the enrolled patients
might have been previously exposed to paclitaxel or other therapeutic agents,
which could cause them to be less sensitive to the Oncogel™. Thus, the results
looked promising enough to continue with the clinical studies to achieve more
reliable results.