Viscum album fermentatum pini versus oral etoposide as adjuvant treatment in osteosarcoma patients after second relapse

Background: Osteosarcoma is a highly malignant bone tumour affecting mainly adolescents.With the recommended neoadjuvant chemotherapy it can be cured in approximately 60% of cases.Few experimental target drugs are currently available through phases I and II trials for relapsed and inoperable patients.We know from historical controls that the risk to relapse increases after the second relapse.Relapse-free survival then decreases to <20% after 12 months.Although no final proof of evidence for oral Etoposide is available, it is often used in clinical practice due to reported good results in advanced childhood cancer with response rates of 15%.Oral Etoposide is well tolerated, easy to administer and affordable.Interferon or MTP-PE (muramyl tripeptide phosphatidyl ethanolamine; Mepact®) have also been used as adjuvant treatment with encouraging results in advanced osteosarcoma (improved disease-free survival [DFS] of 7%) but these treatments are significantly more expensive and less well tolerated.Material and Methods: Viscum album fermentatum Pini (Viscum) is a highly popular herbal medicinal product across central Europe with immunomodulatory activity.Encouraged by the preliminary findings of a pilot study that showed a prolonged DFS of more than 12 months in four out of five with Viscum album treated osteosarcoma patients after their second relapse, we started a two-arm randomized study comparing Viscum album fermentatum Pini s.c.to oral Etoposide in patients free from disease after their second metastatic relapse.Primary end point is the DFS at 12 months compared to a historical group of patients.Results: To date, we have enrolled 17 patients: 8 patients were enrolled in the Viscum arm and 9 patients in the Etoposide arm, 8 female and 9 male, median age 35 years (11 - 65), median follow up 19 months (1 - 42).Median DFS is currently 17.5 months (5 - 42) for the Viscum album arm and 4 months (1 - 12) for the Etoposide arm.Viscum patients had a lower toxicity compared to patients treated with Etoposide.An interim analysis will be done once we have 20 treated study patients (10 for each arm).Conclusions: Viscum album showed promising results as adjuvant treatment in prolonging DFS after a second relapse.It seems to have the same advantages compared to other immunostimulants (IFN, MTPPE) at lower costs.A larger multi-center trial would be desirable to determine efficacy of Viscum therapy in osteosarcoma patients compared to other immunostimulants currently approved in osteosarcoma treatment like Mifamurtide.