Immune-related and adverse events following low versus high initial dose of Viscum album L. in cancer patients

Abstract

Background: Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional therapies in cancer patients in Europe. VA has been associated with improvement in health-related quality of life and a reduction in chemotherapy-related adverse drug reactions (ADRs). Mixed findings have been published regarding effects on overall survival. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Recent evidence regarding immunotherapy in oncology has suggested an association between immune-related ADRs and beneficial outcomes. We investigated the immune-related events and ADR profiles related to VA therapy commencing with a low or high dose. Methods: The medical records of 2393 cancer patients treated between 2000 and 2013 were assessed. Patients were retrospectively divided into two groups based on if their first VA application was low or high according to the appropriate Summary of Product Characteristics. Groups were compared by demographic, disease characteristics, details of treatment and ADRs. Results: 967 patients received a low dose of VA on their first ever application and 1426 patients received a high dose. Groups did not differ by age, but significant differences were observed for gender, type and stage of cancer, type and administration of VA. Commencing VA therapy with a high dose was associated with a higher incidence of ADRs compared to commencing with a low dose (12.6% versus 0.7%). Adjusting for age, tumour site and stage produced an odds ratio of 36.8 (95% CI = 15.4-120.6, p < 0.001). Almost all ADRs, irrespective of dose, were of mild or moderate intensity (low: 100%, high: 94%). The majority of ADRs were immune-related, general disorders and administration site conditions (low: 80%, high: 92%), many of which were desired reactions, such as pyrexia and local reactions. Conclusions: Commencing VA therapy with a high dose was highly associated with ADRs compared to a low dose, however, nearly all ADRs were expected, of mild to moderate intensity and most were desired reactions. Future research will investigate whether higher incidences of immune-related events are indicators of beneficial immunomodulation and thus better clinical outcomes.