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.