Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group

Cancer. 2009 Nov 15;115(22):5339-48. doi: 10.1002/cncr.24566.

Abstract

Background: The addition of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) to chemotherapy has been shown to improve overall survival in patients with nonmetastatic osteosarcoma (OS). The authors report the results of addition of liposomal MTP-PE to chemotherapy for patients with metastatic OS.

Methods: Intergroup-0133 was a prospective randomized phase 3 trial for the treatment of newly diagnosed patients with OS. The authors compared 3-drug chemotherapy with cisplatin, doxorubicin, and high-dose methotrexate (Regimen A) to the same 3 drugs with the addition of ifosfamide (Regimen B). The addition of liposomal MTP-PE to chemotherapy was evaluated.

Results: Five-year event-free survival (EFS) for patients who received liposomal MTP-PE (n = 46) was 42% versus 26% for those who did not (n = 45) (relative risk for liposomal MTP-PE, 0.72; P = .23; 95% confidence interval [CI], 0.42-1.2). The 5-year overall survival for patients who received MTP-PE versus no MTP-PE was 53% and 40%, respectively (relative risk for liposomal MTP-PE, 0.72; P = 0.27; 95% CI, 0.40-1.3). The comparison of Regimen A with Regimen B did not suggest a difference for EFS (35% vs 34%, respectively; relative risk for Regimen B, 1.07; P = .79; 95% CI, 0.62-1.8) or overall survival (52% vs 43%, respectively; relative risk for Regimen B, 1.1, P = .75; 95% CI, 0.61-2.0).

Conclusions: When the metastatic cohort was considered in isolation, the addition of liposomal MTP-PE to chemotherapy did not achieve a statistically significant improvement in outcome. However, the pattern of outcome is similar to the pattern in nonmetastatic patients.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / administration & dosage
  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Infant
  • Infant, Newborn
  • Male
  • Neoplasm Metastasis
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Phosphatidylethanolamines / administration & dosage*
  • Survival Analysis

Substances

  • Immunologic Factors
  • Phosphatidylethanolamines
  • mifamurtide
  • Acetylmuramyl-Alanyl-Isoglutamine