Mistletoe therapy for osteosarcoma


Last update: June 1st, 2022/AT1

Influence of adjuvant mistletoe therapy versus oral etoposide on disease-free survival of osteosarcoma patients after second relapse – a prospective randomised study

Longhi et al. 2009, 2014 [153, 154]

These are two publications of a study which has been published under different aspects in several scientific journals.

Patients and methods

Patients with osteosarcoma who had undergone surgery after their second relapse and were classified as disease-free received in this prospective randomised open-label study either the mistletoe preparation Viscum album fermentatum Pini (Iscador P) or orally administered etoposide. Patients in the etoposide group got 50 mg/m2 oral etoposide daily for a period of 21 days followed by a one-week break for a period of 6 months, and patients in the viscum group received the mistletoe preparation subcutaneously three times a week for a period of 1 year. The study was completed at the beginning of July 2011 due to insufficient recruitment.

The primary objective was defined as the disease-free survival time (DFS) after twelve months, which was to be compared with a historical patient group (DFS: 20 months). Secondary objectives were quality of life and drug safety.


Out of 20 patients enrolled in the study, 9 were randomised into the viscum group and 11 into the etoposide group. At July 2013, DFS had a median of 39 months in the mistletoe therapy group and 4 months in the etoposide group. With regard to the assessment of quality of life, the trend for viscum therapy was also positive; this was particularly evident in the global QoL scale as well as in the "physical function" and "social function" scales. Patients in the viscum group also developed fewer side effects than patients in the etoposide group, resulting in less tiredness, pain, respiratory distress and financial difficulties of the EORTC QLQ-C30. A similar improvement under etoposide could only be observed in the "social function". In contrast, the symptoms of "nausea/vomiting" and "pain" got worse.


Therapy with mistletoe extracts prolonged the disease-free survival time in osteosarcoma patients who had developed a second relapse and improved their quality of life. Despite the small number of patients, the results are significant due to the large difference between the study and the control group.


Last update: January 4th, 2021/AT

Oral etoposide versus Viscum album fermentatum pini as maintenance therapy in osteosarcoma patients with complete surgical remission after second relapse – long-term follow-up of a randomised study

Longhi et al. 2020 [287]

Patients and methods

In relapsed osteosarcoma, the 5-year post-relapse disease-free survival (PRDFS) rate after the second relapse is less than 20 percent. In June 2007, a randomised study was started to compare oral etoposide with Viscum album fermentatum Pini (Iscador P) as maintenance therapy in patients with metastatic osteosarcoma after complete surgical removal after the second relapse. The primary endpoint was the PRDFS rate after 12 months (see above).

This publication now presents the results of a long-term follow-up 12 years after start of the study and a median duration of follow-up of 106 months in 19 treated patients (10 patients in the etoposide group, 9 patients in the Viscum group) or a duration of 83 months taking into account intention-to-treat (ITT) analysis in 20 randomised patients (see above).


On 30th of June 2019, with a median follow-up time (ITT) of 83 months, a median PRDFS of 106 months was detected in the Viscum group in 5 of 9 patients who never relapsed. In comparison, the median PRDFS was only 7 months in the etoposide group, where all patients relapsed (hazard ratio HR 0.287, 95% KI: 0.076-0.884, p = 0.03). Thus, the model prognoses 10-year overall survival rates of 64% in the Viscum and 33% in the etoposide group.


After 12 years from the start of the study, the patients in the Viscum arm continue to show a considerably longer PRDFS compared to oral etoposide, and a trend for an advantage in OS is evident even if the number of treated patients is too small to draw conclusions.


Last update: August 17th, 2020/AT

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