Saroj K Basak1, Alakesh Bera2, Alexander J Yoon3, Marco Morselli4, Chan Jeong1, Anela Tosevska4, Tien S Dong5, Michael Eklund2, Eric Russ2, Hassan Nasser6, Venu Lagishetty5, Rong Guo7, Dipti Sajed8, Sharmila Mudgal9, Parag Mehta9, Luis Avila9, Meera Srivastava2, Kym Faull3, Jonathan Jacobs5, Matteo Pellegrini4,10,11, Daniel Sanghoon Shin10,12, Eri S Srivatsan1,10,11, Marilene B Wang1,6,10. 1. Department of Surgery, Veterans Administration Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California. 2. Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences, Bethesda, Maryland. 3. Pasarow Mass Spectrometry Laboratory, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California. 4. Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, California. 5. Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, Veterans Administration Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California. 6. Department of Head and Neck Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California. 7. Department of Medicine Statistics Core, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California. 8. Department of Pathology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California. 9. Aveta Biomics Inc, Bedford, Massachusetts. 10. Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California. 11. Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California. 12. Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
Abstract
BACKGROUND: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
RCT Entities:
BACKGROUND: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY:Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
Authors: Anela Tosevska; Marco Morselli; Saroj K Basak; Luis Avila; Parag Mehta; Marilene B Wang; Eri S Srivatsan; Matteo Pellegrini Journal: Front Oncol Date: 2022-05-06 Impact factor: 5.738
Authors: Peter Kubatka; Alena Mazurakova; Marek Samec; Lenka Koklesova; Kevin Zhai; Raghad Al-Ishaq; Karol Kajo; Kamil Biringer; Desanka Vybohova; Aranka Brockmueller; Martin Pec; Mehdi Shakibaei; Frank A Giordano; Dietrich Büsselberg; Olga Golubnitschaja Journal: EPMA J Date: 2021-10-06 Impact factor: 6.543