Last update: November 25th, 2021/AT1
Lee et al. 2021 
In this prospective case series, 12 patients with advanced hepatocellular carcinoma were enrolled and data from 10 patients could be analysed. They only received treatment with the mistletoe extract Viscum fraxini-2 (VF-2).
Almost all patients were male, had an average age of 64 years and frequently received therapy with sorafenib or transarterial chemoembolization before mistletoe therapy. The mean duration of treatment with the mistletoe extract was 12.3 weeks (1 to 36 weeks).
While in most patients AFP levels increased before starting therapy with the mistletoe extract, it seemed to stabilise in patients treated for at least four weeks on average within the first three to four weeks. In two patients, AFP levels decreased by more than 30 percent from baseline (37 and 40 percent) and in one patient, this level remained low for 9 months.
The most common side effects were fever, fatigue, rash and local reactions at the injection site (swelling, redness and pressure sensitivity), which slowly resolved within 3 to 5 days after injection.
The case series in patients with advanced hepatocellular carcinoma suggests that mistletoe extract VF-2 may have a potential biological effect in certain patients. However, further research is needed to identify the active agent and predictive markers for response in more detail.
Last update: November 25th, 2021/AT1
Mabed et al. 2004 
This Phase II cohort study conducted at the Oncology Department of Mansoura University in Egypt, included 23 patients (20 men, 3 women) with advanced primary hepatocellular carcinoma. Their tumour was inoperable, they were not eligible for transcatheter-arterial chemoembolization or percutaneous ethanol injection, had no systemic chemotherapeutic pre-treatment and their tumour status was measurable in two dimensions.
They received 2 ampoules of Viscum fraxini-2 s.c. once a week (corresponding to abnobaVISCUM Fraxini 20 mg, diluted to 15 mg with disodium hydrogen phosphate). Physical findings were examined weekly, laboratory values every four weeks, and tumour size was monitored by computer tomography every eight weeks.
Performance status, tumour remission and side effects were recorded according to the World Health Organization (WHO) criteria. The WHO performance status was "1" in 10 patients (44%), "2" in 7 patients (30%) and "3" in 6 patients (26%). The disease was already at an advanced stage in all patients. The median duration of mistletoe therapy was 17 (3 to 152) weeks.
Under mistletoe therapy, there were 3 complete (13%) and 2 partial remissions (9%). Of the complete remissions, one was detected after four months; this patient remained tumour-free for another four months. The other two complete remissions were diagnosed after six months; these patients remained tumour-free for 29 and 38 months, respectively, until publication of the study. In 9 patients* (39%) the tumour growth remained progressive. 9 patients (39%) could not be evaluated because they had died before the end of the observation.
By the time of publication of the study, 3 patients were still alive (2 with complete remission, 1 with a slowly progressive tumour). Median overall survival was 5 (2-38) months, 29 (12-38) months for those patients with complete remission and 6.5 (6-7) months for those with partial remission. The median progression-free interval was 2 (1-38) months for all patients, 29 (8-38) months for those with complete remission and 5 (4-6) months for those with partial remission.
Mistletoe therapy caused fever in 8 patients, local redness in 3 and pain at the injection site in 4. In 3 patients the dosage had to be reduced to 1 ampoule. 1 patient needed analgesics to treat the redness and pain at the injection site. However, in no case the therapy had to be interrupted due to side effects.
In this Phase II cohort study 5 of 23 patients receiving mistletoe therapy alone experienced remissions with tolerable side effects. Despite the small number of patients notably two patients experienced sustained disease-free interval after complete remission.
Last update: January 4th, 2021/AT