Abstract 5582: H1-antihistamines desloratadine and loratadine show potential for cancer therapy

Abstract

Abstract Antihistamines targeting histamine receptor H1make excellent candidates for drug repurposing for cancer therapy: they are safe drugs with minimal side effects that are well tolerated by most people, and evidence that they may be effective against tumors is mounting. Different mechanisms have been proposed for this potential effect: most are thought to be either wholly or partly histamine receptor H1independent, either involving lysosomal cell death or immunological pathways. We have previously found that use of certain H1-antihistamines is associated with substantially improved survival in both breast cancer1and cutaneous malignant melanoma (submitted), and here, we show that a similar association can be seen across multiple tumor types. Linking the cancer register, Drug Prescription Register and Cause of Death Register we have investigated use of the six most common H1-antihistamines used among Swedish cancer patients and survival in 16 different tumor types (n= 602 000), divided into two groups based on whether they have any known response to treatment with anti-immune checkpoint inhibition, such as anti-CTLA-4 or anti-PD-1 (immunogenic vs non-immunogenic tumors). The immunogenic group included cancer of the stomach, colon, rectum or anus, pancreas, lung, breast, prostate, kidney, bladder; and melanoma and Hodgkin lymphoma. The non-immunogenic group included tumors in the uterus, ovaries, brain and CNS, thyroid, liver and biliary tract and non-Hodgkin lymphoma. We choose to study the time period 2005-2014 because immune check point therapy was not yet used and antihistamines still were under patent protection and no off counter prescription occurred.We found that desloratadine use was associated with an improved survival for all the immunogenic tumors, including pancreatic cancer, but none of the non-immunogenic ones. Loratadine use was also associated with improved survival for some of the immunogenic tumors. The other antihistamines studied were consistently not associated with improved survival.Our hypothesis is that our findings have to do with immune checkpoint inhibition, though histamine receptor H1 inhibition as well as lysosomal cell death also may be involved.We believe that there is already a compelling case for initiation of clinical trials of certain H1-antihistamines, foremost among them desloratadine and loratadine, as treatment of both breast cancer and cutaneous malignant melanoma. Based on what we present here, that pool should be extended to include all other immunogenic tumors in our study and priority should be given to trials of desloratadine as treatment of pancreatic cancer, as the prognosis is dismal with highly limited treatment options available, and incidence is increasing. .1. Olsson HL, Einefors R, Broberg P. Second generation antihistamines after breast cancer diagnosis to improve prognosis both in patients with ER+ and ER- breast cancer. Journal of Clinical Oncology. 2015;33(15_suppl):3062-3062. Citation Format: Ildiko Fritz, Philippe Wagner, Hakan L. Olsson. H1-antihistamines desloratadine and loratadine show potential for cancer therapy [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 5582.