Abstract B13: Pilot trial of gemcitabine, nab-paclitaxel, metformin, and a standardized dietary supplement in patients with unresectable pancreatic cancer
Authors: Chung Vincent , Frankel Paul , Shibata Stephen , Mambetsariev Isa , Yin Holly , Mirzapoiazova Tamara , Mambetsariev Bolot , Kulkarni Prakash , Lim Dean , Li Daneng , Chao Joseph , Fakih Marwan , Bild Andrea , Pillai Raju , Adalsteinsson Orn , Hirsh Steven , Salgia Ravi 
Published: March 2020

Abstract
Background: Dietary supplement use has increased over the last decade, and the prevalence is estimated to be 76% of the adult US population as reported by the Council for Responsible Nutrition. However, consistent regular use has only been reported in about 33% of subjects. Pancreatic cancer patients commonly present with weight loss and seek out supplements to improve nutrition but also for any potential anticancer properties that may exist. We conducted a pilot trial to evaluate the tolerability of a standardized combination of dietary supplements with metformin and gemcitabine plus nab-paclitaxel chemotherapy.
Methods: The study was IRB approved at City of Hope. The primary endpoint was feasibility, compliance, and toxicity of the combination with metformin, gemcitabine, and nab-paclitaxel. The secondary endpoints were response rate, PFS, and overall survival. The supplements were formulated to minimize the quantity that patients would need to take and were custom designed by a nutritionally trained oncologist. 17 supplements were given as 12 pills and 2 smoothie packets divided twice per day. Patients began metformin day (D) -6 to evaluate GI tolerance before starting the DS day -3. On day 1, gemcitabine and nab-paclitaxel at standard doses were administered. Serial blood samples were obtained for biomarker analysis and FACT-G questionnaires completed.
Results: 21 patients were accrued and the combination was well tolerated. Grade 3 adverse events (AE) of interest seen in patients include neutropenia 14%, peripheral neuropathy 14%, thrombocytopenia 5%, and fatigue 5%. During days -6 to start of chemotherapy, 7 patients experienced grade 1 gastrointestinal symptoms possibly related to the intervention (3 possibly related to metformin, 2 possibly related to DS/smoothie, 2 possibly related to both), with three also possibly related to disease. 1 patient also reported grade 1 dizziness possibly related to DS/smoothie. The median progression-free survival and overall survival were 5.4 months (95% CI 1.5-10.9) and 8.9 months (95% CI 2.2-18.4), respectively. 6 patients (29%) achieved a partial response. 14 patients reported on FACT-G quality of life changes between start of metformin and Day 1 of cycle 1. Overall FACT-G score decreased in 9 patients, was unchanged in 1 patient, and improved in 4 patients. RNA was extracted from PBMC and run with NanoString Immune Profiling and PanCancer Pathway. Preliminary observation includes the best response is associated with initial decreased expression of myc and IL7R, also downregulation in TGF-B, MAPK, and Wnt pathways. Additional analysis in ongoing.
Conclusions: Pancreatic cancer patients commonly have gastrointestinal issues that may affect tolerance to treatment. Our trial showed the combination of chemotherapy and dietary supplements was feasible. The common grade 3 AEs were less frequent than observed in the MPACT trial; however, this is a small study and additional trials would need to be done to confirm this. (ClinicalTrials.gov Identifier: NCT02336087.)
Citation Format: Vincent Chung, Paul Frankel, Stephen Shibata, Isa Mambetsariev, Holly Yin, Tamara Mirzapoiazova, Bolot Mambetsariev, Prakash Kulkarni, Dean Lim, Daneng Li, Joseph Chao, Marwan Fakih, Andrea Bild, Raju Pillai, Orn Adalsteinsson, Steven Hirsh, Ravi Salgia. Pilot trial of gemcitabine, nab-paclitaxel, metformin, and a standardized dietary supplement in patients with unresectable pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B13.