Osteosarcoma: The Same Old Drugs or More?

Evaluation of treatment strategies in osteosarcoma has historically been a controversial subject. In the early 1980s, many outstanding investigators argued both for and against the utility of adjuvant chemotherapy. 1-4 This issue was eventually settled when prospective randomized trials demonstrated superior outcome for patients receiving adjuvant treatment. We are now faced with a similar controversy regarding the role of an adjunct to conventional chemotherapy. Meyers et al 5 and the Children's Oncology Group are to be congratulated on the largest ever completed randomized trial in osteosarcoma. After more than 20 years of stagnation with conventional chemotherapy, their report seems to suggest that liposomal muramyl tripeptide ethanolamine (MTP), an immune modulator, improves the overall survival for patients with this disease. In this trial, INT0133, 662 young patients with localized, resectable osteosarcoma were randomly assigned to high-dose methotrexate, cisplatin, and doxorubicin plus ifosfamide in a 2 2 factorial design which also included a randomized evaluation of MTP. 5,6 Several osteosarcoma groups have obtained their best results using ifosfamide-containing regimens. 7 In the schedule used by the authors, however, the addition of ifosfamide neither enhanced eventfree survival (EFS) nor overall survival. 5,6 Before abandoning ifosfamide from osteosarcoma chemotherapy, however, it should be noted that cisplatin was omitted from preoperative chemotherapy in the ifosfamide-containing arm of INT0133, so that evaluation of the role of ifosfamide was hampered due to the lack of clarity as to its contribution as a substitute or adjunct.