In recent preclinical studies of ADH-1 in combination with chemotherapy, Adherex has seen reproducible and significant synergistic anti-tumor activity. In preclinical melanoma studies conducted at the Duke Comprehensive Cancer Center for example, when systemic ADH-1 was given in combination with regionally infused melphalan (a generic chemotherapy typically used in this setting), all of the animals on study achieved complete remission of their tumors, and the tumors did not return during the entire two-month timeframe of the studies. [Augustine CK et al. Targeting N-Cadherin Enhances Antitumor Activity of Cytotoxic Therapies in Melanoma Treatment. Cancer Res 2008;68(10);1-8.].

 

 

 

Caption: In the upper graph and left-hand photo, animals treated with melphalan alone experienced some intermediate anti-tumor effect, but the majority of the tumors started to regrow after 10 days. In the lower graph and right-hand photo, each of the animals received a combination of melphalan and ADH-1 and all were complete responders for the entire duration of the studies (60 days).

 

A similar study was conducted in a melanoma animal model that was resistant to treatment with melphalan. The combination of melphalan and ADH-1 again showed striking synergistic effect, with significant tumor growth delay despite the established resistance of these tumors to treatment with melphalan alone.

 

 

Caption: The top panel represents the control model - systemic saline plus regional saline - with days after treatment on the x-axis and increase in tumor growth on the y-axis. As shown in this panel, all of the tumors grow out of control. The second panel shows ADH-1 alone given systemically and, again, all of the tumors grow. The third panel shows regional melphalan alone; once again all of the tumors grow. The bottom panel shows the combination of systemic ADH-1 and regional melphalan. Here, several of the animals show striking tumor shrinkage or markedly prolonged times before tumor growth occurs.