Abstract 1732: Hybrid-nanoengineering of an effective combination therapy for pancreatic cancer

Abstract

Abstract Introduction: A novel proprietary nano-combination therapy (Hybrid-Nanoengineering) combination of paclitaxel and bioavailable curcumin (nano-paclitaxel-curcumin or NPC) has been created and shown to be stable as a dry powder and was effective in treating pancreatic cancer in preclinical models. Experimental Methods: The highly aggressive L3.6PL model of orthotopic pancreatic cancer is typically lethal within 30 days. Three L3.6PL tumor spheroids were introduced into the pancreas of each of 40 nude mice with a vehicle control and treatment group. On 5 of the 20 mice in each treatment group 5x105 cells were implanted to act as sentinels for the orthotopic growth. After 5 days, treatment was initiated with 10 mg/kg (paclitaxel equivalent) every 4 days. The NPC was resuspended with saline to a 1 mg/ml final concentration and the vehicle group received saline (VC) in an equivalent volume. The NPC dose was adjusted on day 17 to 20 mg/kg, q4d as there was no observed flank tumor growth inhibition. Treatment was continued for 25 days before treatment was halted on day 42. Results 1: Tumor response was low at the initial 10 mg/kg dose and after 12 days when the flank tumors had reached ~600 mm3, the treatment was adjusted to 20 mg/kg, q4d. 17/20 of the VC control animals died or were euthanized by day 42, whereas in the NPC group 13/20 animals survived for an unexpected 65% survival rate with this aggressive tumor. The mean orthotopic tumor weight was 2.53 g and 0.81 g for the VC and NPC groups respectively, indicating a significant reduction in tumor volume with treatment in addition to the significant survival benefit with the NPC drug treatment. Results 2: At day 42 a decision to halt the combination therapy was made and two groups of 5 were randomized from the surviving NPC group animals. One group received a nano-curcumin (NC) at 40 mg/kg, q4d and one no treatment (C) for an additional 23 days. Tumors were excised and the average tumor volumes were 1.39 g for the "C" group and 0.54 g for the "NC" animals. Discussion: The NPC formulation provided dramatic and unexpected survival benefit at a relatively low dose of paclitaxel and was well tolerated by the mice already burdened with an aggressive pancreatic tumor. In fact, by allowing the tumors to escape initially at the 10 mg/kg, q4d dose, and reaching nearly 600 mm3 (flank sentinel tumors), this was an extreme challenge and the 20 mg/kg, q4d dose provided a significant benefit to overall survival, tumor burden and animal health. In a previous study with Panc-1 xenograft tumors, a clear benefit was shown with the nano-paclitaxel-curcumin over nab-paclitaxel with similar tumor volumes at half the dose (not shown). Citation Format: Mewa Singh, Michael R. Briggs. Hybrid-nanoengineering of an effective combination therapy for pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1732.