MISTOSUS: a phase II trial of Viscum album extract adjuvant therapy for relapsed resectable osteosarcoma

Relapsed resectable osteosarcoma carries a dismal prognosis of 30% 12-month post-relapse event-free survival (PREFS-12). Surgery remains the primary therapy for metastatic pulmonary osteosarcoma with the role for adjuvant therapy still undefined. There is an urgent need for effective nontoxic adjuvant therapies to improve PREFS following complete resection of metastases. Viscum album extract (Iscador® P, Iscador AG, Arlesheim, Switzerland) is a fermented aqueous extract manufactured from the leaves, stems, and berries of the white-berried hemiparasitic plant from the European mistletoe (Viscum album L.) grown on pine trees (P = Pini). It is a promising therapeutic antineoplastic agent with preclinical and clinical evidence of benefit in osteosarcoma. This includes a pilot study showing 55% PREFS in 9 pediatric, adolescent and young adult (AYA) patients with a median follow-up of 84 months. Viscum album extract has a long history of use in Europe and a track record of safety in children which allowed for the opening of a Phase II trial in the US to test the efficacy of Viscum album extract to improve PREFS in children and AYAs with relapsed osteosarcoma. Secondary outcomes include effects on quality of life and changes in immune profiling of tumor and serum samples. Osteosarcoma is the most common bone cancer in children, teenagers, and young adults. When osteosarcoma comes back in the lungs after treatment, the chance of survival is low, even when the cancer can be taken out with surgery. Using chemotherapy after surgery to stop the cancer from coming back has not had much success. There is an urgent need for safe therapies that work well to help these patients to live longer, free of cancer. Viscum album extract (Iscador P, Iscador AG, Arlesheim, Switzerland) is a mistletoe extract manufactured from the leaves, stems, and berries of the white-berried plant, Viscum album L. grown on pine trees (P = Pini). It is a promising cancer-fighting medicine with good results in lab experiments and small clinical trials for patients with osteosarcoma. A recent small study in Italy showed that 55% of patients taking this medication did not have their cancer return within a year. For most of these patients, they were cancer free, 7 years later. Viscum album extract has been used for decades in Europe and has a track record of safety in children and adults. This paved the way for starting a clinical trial in the United States to test the use of Viscum album extract for children, teenagers, and young adults with osteosarcoma that has come back and can be removed with surgery. Another goal of this study is to describe what changes this medicine may have on quality of life, the immune system, and blood tests during treatment.