Volume 7, Supplement 1, 25 September 2015, Pages 5
Introduction:
Mistletoe extracts have anti-tumoral properties in vitro and in animal
studies and are approved for subcutaneous use in cancer patients.
Intravenous application, which has been used off label occasionally, may
allow higher systemic concentration of active substances and may
therefore be better efficacious. The aim of this study was, to determine
the maximum tolerable dose (MTD) and safety of intravenous application
of a commercial mistletoe extract.
Methods: Helixor P, an aqueous extract from white-berry pine mistletoe (Viscum album
L. subspecies austriacum), was solved in 250 ml physiological saline
and infused in three hours’ time weekly for 3 weeks in patients with
advanced cancer. The classical phase I 3 + 3 dose escalation scheme was
followed. Predefined dose groups were 200, 400, 700, 1,200 and 2,000 mg.
If 3 patients tolerated the first dose (200 mg), the next three
patients received the next dose (400 mg) and so forth. Maximum planned
dose was 2000 mg. Weekly during the treatment and 1 week later (week 4)
tolerability, clinical status, routine safety laboratory parameter and
adverse events were documented. The study was performed according to
good clinical practice (GCP).
Results:
18 patients (3 in the dose groups 200, 400, 700 and 1200 mg,
respectively, 6 in the dose group 2000 mg) were included and finished
the study. MTD was not reached. Because one dose limiting toxicity
(DLT), an allergic reaction, occurred during infusion of 2000 mg, three
more patients had to be included in this dose group and tolerated it
well. Two patients in the dose group 2000 mg reported mild to moderate
fever. Liver enzymes and other laboratory parameters changed or became
abnormal in some patients but no systematic changes could be observed
and most changes of the laboratory parameters could be related to other
reasons.
Conclusions:
Weekly infusion of Helixor P was tolerated up to a starting dose of
2000 mg. In this dose group an increased risk for side effects (allergic
reaction, mild to moderate fever) has to be expected.
Copyright © 2015 Published by Elsevier GmbH
