Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations

Abstract

Combination strategies involving chemotherapy and monoclonal antibodies (mAb) are commonly used in attempts to produce better clinical outcomes. This practice has led to new and ongoing toxicities that may lead to reductions in dose or noncompliance, limiting the effectiveness of treatment. Viscum album L (VA) preparations are widely used in Europe as additive therapy and have been associated with reduced chemotherapy-related adverse reactions and increased health-related quality of life. Concomitant VA therapy might also reduce toxicity related to mAb. This retrospective study investigated the safety of combined treatment with VA and mAb in cancer patients. A total of 43 patients had combined therapy (474 exposures); 12 had VA without mAb (129 exposures), and 8 had mAb without VA (68 exposures). Most patients (89.3%) received concomitant chemotherapy or supportive therapies. A total of 34 patients (60.7%) experienced 142 adverse events (AEs). Leucopenia (14.1% of all events), acneiform rash (8.5%), and stomatitis (6.3%) occurred most frequently. Longitudinal logistic regression analysis suggested a nearly 5 times higher odds of experiencing an AE following treatment with mAb compared with mAb plus VA (95% CI = 1.53-16.14). Our results, together with theoretical consideration of potential botanical-drug interactions, suggest that combined treatment with VA and mAb is safe.

Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer

“…Thus, the immunomodulatory nature of VA raises the question of whether there are immunologic interactions between VA and inhibitors of the PD-1/PDL-1 or CTLA-4 pathways that might lead to increased toxicity for cancer patients. On the other hand recent results of our group revealed that the adverse event rate of targeted therapy was significantly reduced in cancer patients when VA was concomitantly applied [30]. This is in line with the observation that VA is applied in integrative oncology concepts concomitantly to adjuvant antineoplastic treatment to improve tolerability of chemotherapy-induced toxicity [24,39,40].…”

“…With regards to adverse effects the safety profile of VA has indicated that subcutaneous (s.c.) and intravenous (i.v.) applications of VA in cancer were safe with no serious AEs [30][31][32][33]. A meta-analysis of clinical studies that applied VA Iscador preparations concluded that it might have beneficial effects in psychosomatic self-regulation in addition to short-term quality of life-improving effects in cancer patients [34].…”

Die Misteltherapie in der Behandlung von Patienten mit einer Krebserkrankung

“…Die Ergebnisse einiger weniger hierzu bisher durchgeführter Untersuchungen weisen darauf hin, dass Mistelextrakte kein oder nur ein geringes Risiko für klinische Interaktionen aufweisen. Es handelt sich dabei vorwiegend um präklinische Studien [40][41][42][43][44][45][46]. Eine erste Phase-I-Studie zeigte für ein Mistelpräparat am Patienten, dass die Pharmakokinetik des Zytostatikums Gemcitabin bei paralleler Anwendung von hohen Dosierungen bis zu 250 mg Mistelextrakt nicht beeinflusst wurde [47].…”

Brokkoli bei Pankreaskarzinom – welche Dosis?

“…Außerdem bestärkt diese Untersuchung, dass man eine Misteltherapie sehr gut auch parallel zur Chemotherapie einsetzen kann. Dies konnten bereits andere Studien zeigen, nämlich dass keine Wechselwirkungen zwischen einer Misteltherapie und einer schulmedizinischen Therapie über bestimmte Leberenzyme der Cytochrom-P450-Gruppe zu erwarten sind [7,8] und dass eine Misteltherapie während einer Checkpointinhibitorund Antikörpertherapie eingesetzt werden kann [9,10].…”