A randomized study with adjuvant mistletoe versus oral Etoposide on post relapse disease-free survival in osteosarcoma patients

Background: Osteosarcoma is a highly malignant bone tumor affecting mainly adolescents. While it can be cured in approximately 60% of cases with the recommended neoadjuvant chemotherapy, 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% at 12 months. Oral Etoposide is often used in clinical practice but outside any protocol or evidence of improved survival. Methods and Materials: Viscum album fermentatum Pini (Viscum) is a highly popular phytocompound across central Europe with immunomodulatory activity. Encouraged by the preliminary findings of a pilot study that showed a prolonged disease-free survival (DFS) of more than 12 months in four of our five osteosarcoma patients after their second relapse, we started a two-arm randomized study comparing Viscum album fermentatum Pini s.c. to oral Etoposide for patients free from disease after their second metastatic relapse. Our aim is to compare the disease-free survival to a historical group of patients at 12 months. Results: To date, the median follow-up is 9.5 months while the study is in progress. The median DFS is currently 3 months for Etoposide and 8.5 months for Viscum. Patients on Viscum report a higher quality of life due to lower toxicity, compared to Etoposide. Conclusion: In-depth study of the immunomodulatory mechanisms of Viscum in osteosarcoma patients is required. Viscum shows promise as adjuvant treatment in prolonging DFS after a second relapse, while Etoposide does not seem to prolong the DFS in patients after their second relapse. A larger multi-center trial is required to determine efficacy of therapy in osteosarcoma patients. Preliminary data are reported. (C) 2009 Elsevier GmbH. All rights reserved.