Celsion Corporation, has announced the publication of a clinical and scientific review of ThermoDox®, the Company's proprietary heat-activated liposomal encapsulation of doxorubicin, as a treatment for Hepatocellular Carcinoma (HCC or primary liver cancer) in the August 2011 issue of Future Oncology (Volume 7, Number 8).
The article, titled "Lyso-Thermosensitive Liposomal Doxorubicin: An Adjuvant to Increase the Cure Rate of Radiofrequency Ablation (RFA) in Liver Cancer," provides an overview of current standards and investigational approaches to the treatment of HCC, focusing on the curative and synergistic potential of combining lyso-thermosensitive liposomal doxorubicin (LTLD or "ThermoDox®") and RFA as front-line therapy.
Ronnie T.P. Poon, MD (QMH), MS, PhD, FRCS (Edin), FACS, Professor of Surgery at the University of Hong Kong and a Lead Asia Pacific Principal Investigator in Celsion's pivotal Phase III HEAT Study of ThermoDox® in primary liver cancer, and Nicholas Borys, MD, Celsion's Chief Medical Officer, were co-authors of the article, which is available online (http://www.futuremedicine.com/doi/abs/10.2217/fon.11.73).
"The clinical potential of ThermoDox® in HCC stems from a number of properties, including the known efficacy and tolerability of doxorubicin in HCC, the enhancement of cell killing when doxorubicin is combined with hyperthermia, localization of ThermoDox® in tumors and tumor vasculature and rapid release of drug in the treatment area only when triggered by heat," said Dr. Poon.
Dr. Poon continued, "These properties are designed to extend the therapeutic benefit of RFA, a treatment whose efficacy is significantly influenced by size, to larger tumors. If this curative and synergistic potential is borne out in the Phase III HEAT Study, a rational future strategy for larger HCC legions is to employ RFA and ThermoDox® as front-line therapy."
Dr. Borys added: "No more than 30 percent of HCC patients are considered suitable for curative treatment because of tumor size, severity of liver impairment and other factors, leading to a high rate of mortality for this globally epidemic disease. We believe that ThermoDox®, as an adjuvant therapy that interacts synergistically with RFA, may represent one of the most important new treatment advances for primary liver cancer. Having met the enrollment objective in our Phase III HEAT Study, we remain diligent in our efforts to support the highest level of study execution ahead of a planned interim analysis by an independent Data Monitoring Committee and final data readout."
The article in Future Oncology details the clinical activity, safety and tolerability, mechanisms of action and pharmacokinetic properties of ThermoDox®, as well as strategies to improve RFA treatment for HCC. Among the properties highlighted in the article are:
• ThermoDox®, as a liposome, rapidly concentrates in the liver and spleen. As tumors have much higher microvascular permeability than normal tissue, ThermoDox® further accumulates in liver tumors;
• Hyperthermia has a biological effect of increasing the pore size in tumor blood vessels and therefore enhancing the extravasation of liposomes into the tumor interstitium;
• ThermoDox® is over 1,000 times less permeable across normal blood vessels than free doxorubicin, offering less potential for systemic toxicity;
• Hyperthermia has been shown to preferentially increase liposomal permeability within the microvasculature in tumor versus normal tissue;
• The optimal liposome size for heat-induced extravasation was found to be 100 nm, the mean diameter of ThermoDox®.
The article also describes results from a Phase I study of ThermoDox® in 24 patients with HCC or liver tumors metastatic from other primary sites. The trial established a statistically significant dose-response effect and a maximum tolerated dose (MTD), 50mg/m(2), for further study.
Mean time to treatment failure for patients receiving at least the maximum tolerated dose was 374 days, while that for patients receiving less than 50 mg/m(2) was 80 days. Drug-related adverse events were consistent with the adverse event profile of systemic doxorubicin.