Written by ι Stock Market Media Group Staff — June 6, 2013
Nuvilex, Inc. (OTCQB: NVLX) has a technology in its cell encapsulation process that will very likely play some role in the future of oncology. How large that role will be is contingent upon the technology continuing to return solid results when it’s put to the test. One such area where the technology has had a chance to prove its worth is in a preclinical study that was reported in the highly respected scientific publication, International Journal of Cancer.
In that study Nuvilex’s cell encapsulation was used together with the well-known anticancer drug ifosfamide and radiation for the treatment of pancreatic tumors in rats. The type of cells encapsulated for the study were the same as those used in the company’s two independent Phase II clinical trials in patients with advanced, inoperable pancreatic cancer. These cells are used because of the highly elevated activity of CYP2B1, the ifosfamide-activating enzyme.
Before the FDA’s approval of Eli Lilly’s blockbuster drug Gemzar (gemcitabine) in the late 1990s, many patients with advanced, localized inoperable pancreatic cancer were treated with the combination of 5-fluorouracil (5-FU) and radiation. When we talk about “localized” cancers, we mean the cancer has not metastasized, or spread, to distant organs such as the liver. After Gemzar was approved, it replaced 5-fluorouracil, and together with radiation became the “treatment of choice” in the US for many patients with inoperable, localized, advanced pancreatic cancer.
This study using Nuvilex’s technology was to discover if the cell encapsulation/ifosfamide treatment could work on the preclinical level – one day potentially being effective in combination with radiation as a multimodality treatment of patients with inoperable, localized, advanced pancreatic cancer. And, much like the cell encapsulation/ifosfamide treatment could one day replace Gemzar as the worldwide standard of care as a single agent for pancreatic cancer, it could also prove to be the “base” upon which combination chemotherapy treatments for the disease can be built.
Multimodality therapies can consist of any combination of surgery, chemotherapy, and radiation treatment. Obviously, in the case of inoperable advanced pancreatic cancer, the only option for multimodality therapy is the combination of chemotherapy and radiation, also known as chemoradiation, or radiochemotherapy.
Often the choice of the chemotherapy drug used in radiochemotherapy regimens is made not only because the drug “kills” the cancer cells (as does the radiation therapy), but also because the chosen drug can act as a “radiosensitizer”— meaning the drug enhances the beneficial (tumor-destructive) effects of the radiation.
In the preclinical study, the principal author was Dr. Matthias Löhr, who served as the Principal Investigator for Nuvilex’s Phase II trials in pancreatic cancer. During the study, pancreatic cancers were induced in rats by inoculating them with DSL6A pancreatic cancer cells – DSL6A was an established cell line derived from a rat pancreatic cancer. After introducing the cancer to the rats, treatment was started 10-12 weeks later when the tumors had grown to a size of 10-15 mm. All of the test subjects in the study were injected with 50 capsules containing approximately 50,000 cells.
The rats in the study were divided into four groups according to treatment:
(1) encapsulated cells alone – these served as the “control” group, (2) encapsulated cells plus ifosfamide only, (3) encapsulated cells plus radiation only, and (4) encapsulated cells plus the combination of ifosfamide and radiation.
Results of the study showed that cell encapsulation plus ifosfamide together with radiation gave the earliest beneficial response to treatment and the greatest percentage of responders of any of the 4 treatment groups. In addition, the plasma concentration of Tumor Necrosis Factor- alpha (TNFα) was significantly reduced by the cell encapsulation/ifosfamide plus radiation multimodality treatment. TNFα has been shown to have a tumor-promoting role in various types of cancers in animals and in humans and may increase the metastasis of certain cancers. For example, patients suffering from metastatic pancreatic cancer have high levels of TNFα in their blood. The lowering of TNFα levels by the combination of cell encapsulation/ifosfamide plus radiation therapy lends credence to the belief that this multimodal treatment might be effective against pancreatic cancer. Thus, Nuvilex’s cell encapsulation continues to deliver results that show it could be a better solution than Gemzar for pancreatic cancer patients when combined with ifosfamide.
Several clinical trials that discuss the use of the combination of Gemzar plus radiation versus Gemzar alone for the treatment of localized disease have appeared over the years, but the results have been somewhat equivocal. This data, which has been left open to interpretation, in concert with the results of other studies of combined chemotherapy and radiation led Dr. Philip Agop Philip of the Karmanos Cancer Institute at Wayne State University in Detroit, to comment in an editorial in the Journal of Clinical Oncology that he believes “…there is an urgent need to test newer and novel treatment strategies in patients with pancreatic cancer including those with localized, advanced pancreatic cancer.”
Given this call to test newer and novel treatment strategies, it begs the question is it possible that Nuvilex’s cell encapsulation/ifosfamide treatment could be effective in combination with radiation as a multimodality treatment of patients with inoperable, localized, advanced pancreatic cancer?
Interestingly, in Nuvilex’s Phase II trials using its cell encapsulation/ifosfamide treatment, an ancillary finding to the efficacy on the primary tumor was: “beneficial effects on metastatic tumors in the liver were also observed.” This according to the authors of a review article entitled “Encapsulated cells to focus on the metabolic activation of anticancer drugs” which appeared in the scientific publication, Current Opinion in Molecular Therapeutics in 2010. The finding is in addition to the beneficial effects on the primary tumor, of course.
It is this finding that has us asking an additional question with regard to Nuvilex’s cell encapsulation/ifosfamide treatment being effective in combination with radiation as a multimodality treatment. Could that multimodality therapy play a role in the treatment of advanced, inoperable pancreatic cancer that is no longer localized and has metastasized to the liver as well?