Kavindra Nath1, David S. Nelson1, Andrew M. Ho1, Stephen B. Pickup1, Rong Zhou1, Dennis B. Leeper2, Jerry D. Glickson1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States; 2Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States
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.