DB-1 Human Melanoma Xenograft PH and Energy State Changes During Treatment with Lonidamine Plus Melphalan

Kavindra Nath¹, David S. Nelson¹, Andrew M. Ho¹, Stephen B. Pickup¹, Rong Zhou¹, Dennis B. Leeper², Jerry D. Glickson¹

Synopsis: Since acidification enhances the activity of nitrogen mustard alkylating agents, as well as of platinum drugs such as cisplatin (CPT) that act by similar mechanisms (adding substituents to and cross-linking DNA), we have evaluated the effect of lonidamine (LND)-induced tumor acidification and response of DB-1 melanoma xenografts to treatment with CPT (7.5 mg/kg, i.v.) or melphalan (LPAM; 7.5 mg/kg, i.v.). This dose of CPT had no effect on tumor growth. Only LND + LPAM produced a significant growth delay of 19.9 2.0 d compared to LND alone of 1.1 0.1 d and LPAM alone of 4.0 0.0 d. These studies point to the potential feasibility of multiple-dose treatment of systemic melanoma by combination chemotherapy with LND + LPAM.