Osteosarcoma: The Addition of Muramyl Tripeptide to Chemotherapy Improves Overall Survival—A Report From the Children's Oncology Group

TLDR

The study compared standard three‑drug chemotherapy with a four‑drug regimen and evaluated whether adding muramyl tripeptide (MTP) improves event‑free and overall survival in newly diagnosed osteosarcoma patients. Patients received identical cisplatin, doxorubicin, and methotrexate doses with surgery, then were randomized in a 2×2 factorial design to receive ifosfamide and/or MTP, with event‑free and overall survival as primary endpoints. Adding MTP to chemotherapy increased 6‑year overall survival from 70% to 78% (HR 0.71, 95% CI 0.52–0.96) and showed a non‑significant trend toward improved event‑free survival, while ifosfamide added no benefit.

Abstract

To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma.Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design. The primary end points for analysis were EFS and overall survival.In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96).The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.