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- Fritz, Ildikó, et al.
(författare)
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Desloratadine and loratadine stand out among common H1-antihistamines for association with improved breast cancer survival
- 2020
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 59:9, s. 1103-1109
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Tidskriftsartikel (refereegranskat)abstract
- Background: As tumors maintain an inflammatory microenvironment, anti-inflammatory medication can be useful in cancer therapy. We have previously shown an association with improved survival in melanoma for use of the H1-antihistamines desloratadine and loratadine, and here we examine use of H1-antihistamines and breast cancer mortality.Material and methods: We investigated use of the six major H1-antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) and breast cancer-specific and overall mortality in a nation-wide register-based study of all 61,627 Swedish women diagnosed with breast cancer 2006-2013. Both peri- and post-diagnostic antihistamine use was analyzed using Cox regression models. Analyses were stratified for age and subgroup analyses based on estrogen receptor status and menopausal status were performed.Results: We found a consistently improved survival of desloratadine users (HR = 0.67; 95% CI 0.55-0.81, p < .001), as well as of loratadine users (HR = 0.80; 95% CI 0.67-0.95, p = .012), relative to nonusers, regardless of patient age, menopause, estrogen receptor status or stage of the tumor, or whether breast cancer-specific or overall survival was analyzed. The survival of users of other antihistamines varied relative to non-users.Conclusion: Based on their safety and current use within the patient population, together with our observations, we suggest the initiation of trials of desloratadine and loratadine as treatment of breast cancer as well as studies of the mechanism behind their possible effect. Further studies on any effects of other H1-antihistamines may also be merited, as well as of H1-antihistamine use and survival in other malignancies.
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| 2. |
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| 3. |
- Fritz, Ildikó
(författare)
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Improved cancer survival with use of common antihistamines. Epidemiological studies on the use of H1-antihistamines and survival in cancer.
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer often results from chronic inflammation, and anti-inflammatory medications are therefore potential candidates for drug repurposing for cancer therapy. H2-antihistamines such as cimetidine have long been studied for their promise as cancer medications, but H1-antihistamines have thus far not been studied widely for this purpose. We have previously shown an association with improved breast cancer survival for use of some H1-antihistamines, and other studies have shown similar results for non-localized cancer, non-small cell lung cancer and ovarian cancer, while evidence is mounting that some H1-antihistamines normally used to alleviate allergic reactions may also have anti-tumor effects. In the four studies that form the basis of this dissertation, we show that some of the most commonly used H1-antihistamines in Sweden – desloratadine and loratadine – are associated with substantially improved survival for patients with melanoma (Study I), breast cancer (Study II) as well as several other immunogenic tumor types (Study III) and quantify the potential effect of a desloratadine intervention, showing that numerous lives may be spared should desloratadine be integrated into cancer therapy (Study IV). We suggest a desloratadine effect as the explanation of our findings, one that is likely immunological in nature, and call for randomized clinical trials of desloratadine as treatment of immunogenic cancers, and if effective, further studies to quantify and elucidate the mechanism.
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| 4. |
- Fritz, Ildikó, et al.
(författare)
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Improved survival in several cancers with use of H1-antihistamines desloratadine and loratadine
- 2021
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Ingår i: Translational Oncology. - : Elsevier BV. - 1936-5233. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously shown an association with substantially improved survival in breast cancer and melanoma for desloratadine and loratadine users, and set out to find whether an improved survival can be seen in tumors with and without a known response to immune checkpoint therapy, such as anti-CTLA-4 or anti-PD-1. Methods: We investigated survival and use of six common H1-antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) in a nation-wide cohort of all 429,198 Swedish patients with ten types of immunogenic (gastric, colorectal/anal, pancreatic, lung, breast, prostate, kidney, and bladder cancer, melanoma and Hodgkin lymphoma) and six non-immunogenic (liver, uterine, ovarian, brain/CNS, and thyroid cancer and non-Hodgkin lymphoma) tumors diagnosed 2006–2017. Follow-up was until 2019–02–24. Findings: Desloratadine use was associated with an improved survival for all immunogenic tumors, but not for the non-immunogenic ones. Loratadine use was associated with improved survival for some tumors. Use of the other antihistamines could not be shown to be consistently associated with improved survival to a statistically significant degree. Interpretation: Our hypothesis is that our findings result from immune checkpoint inhibition, and we believe both desloratadine and loratadine should be tested in randomized clinical trials as treatment of immunogenic tumors, with priority given to trials of desloratadine as treatment of tumors with few therapy options and dismal prognoses, such as pancreatic cancer. If our results can be confirmed in a clinical setting, new, potentially curative, therapies could result for several tumors, including ones with dire prognoses and limited treatment options.
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| 5. |
- Fritz, Ildikó, et al.
(författare)
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Lung cancer in young women in southern Sweden : A descriptive study
- 2018
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Ingår i: Clinical Respiratory Journal. - : Wiley. - 1752-6981 .- 1752-699X. ; 12:4, s. 1565-1571
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Lung cancer, a common malignancy and cause of cancer-related deaths, is strongly linked to several environmental exposures, and thus primarily affects the elderly. Formerly a man's disease, its incidence is rising among women, and lung cancer is now more common in women than men in Sweden. Women are particularly over-represented among young patients. While overall cancer mortality in Europe is decreasing, female lung cancer mortality is increasing. Objectives: We describe the epidemiological presentation of lung cancer in young Swedish women, aiming to pinpoint its risk factors for young women. Methods: 1159 women with newly diagnosed lung cancer in southern Sweden 1997-2015 answered questionnaires on their lifestyles and personal and family medical histories. We identified those below age 50. Results: 70 (6.0%) of 1159 women were below age 50. Most (n = 49, 70.0%) were aged 45-50; eight (11.4%) were below age 40. The most common lung cancer subtype was adenocarcinoma (n = 33, 47.1%). 12.9% (n = 9) had carcinoid tumors. Most women reported both first- and second-hand tobacco smoke exposure (n = 54, 77.1%); 2.9% (n = 2) reported neither. 17.1% (n = 12) were never-smokers. 34.3% (n = 24) reported frequent X-ray radiation exposure. 78.6% reported at least one near relative with cancer. 25.7% reported relatives with lung cancer. Conclusions: Lung cancer remains rare in young women, and tobacco smoke exposure is the single greatest risk factor, even for never-smokers. Thus, avoiding tobacco smoke exposure remains the most important preventive measure against lung cancer for young women in Sweden and elsewhere.
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| 6. |
- Helgadottir, Hildur, et al.
(författare)
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Multiple primary melanoma incidence trends over five decades, a nation-wide population-based study
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 113:3, s. 318-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Over the past decades many regions have experienced a steady increase in the incidence of cutaneous melanoma. Here, we report on incidence trends for subsequent primary melanoma.METHODS: In this nationwide population-based study, patients diagnosed with a first primary cutaneous melanoma reported to the Swedish Cancer Registry, were followed for up to ten years for a diagnosis of subsequent primary melanoma. Patients were grouped with patients diagnosed with first melanoma in the same decade (1960s, 1970s, 1980s, 1990s and 2000s, respectively). Frequencies, incidence rates (IRs), standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for second melanomas were calculated. All tests of statistical significance were two-sided.RESULTS: 54,884 patients with melanoma were included and 2,469 were diagnosed, within ten years, with subsequent melanomas. Over the five decades there was a statistically significant steady increase in the frequency, IR and SIR for second primary melanoma. For example, in the 1960s cohort, <1% (1.0 (95% CI = 0.5-1.7) and 1.1 (95% CI = 0.5-1.9) per 1,000 person-years in women and men, respectively) had second primary melanoma and this rose to 6.4% (7.5 (95% CI = 6.8-8.3) per 1,000 person-years) in the women and 7.9% (10.3 (95% CI = 9.3-11.2) per 1,000 person-years) in the men in the 2000s cohort. This rise was seen, independent of age, sex, invasiveness or site of the melanoma. Further, in patients diagnosed with a second melanoma, the frequency of those having >2 melanomas increased statistically significantly and was 0.0% in the 1960s and rose to 18.0% in the 2000s (P <.001).CONCLUSIONS: This is the first study to evaluate and report on a rising trend for subsequent primary melanoma. Additional primary melanomas worsen the patients' survival and precautions are needed to turn this steep upgoing trend.
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