Faculty Collaboration Database

Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol 2005 Mar 20;23(9):2004-11

Date

03/19/2005

Pubmed ID

15774791

DOI

10.1200/JCO.2005.06.031

Scopus ID

2-s2.0-20144380941 (requires institutional sign-in at Scopus site)   623 Citations

Abstract

PURPOSE: To determine whether the addition of ifosfamide and/or muramyl tripeptide (MTP) encapsulated in liposomes to cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) could improve the probability for event-free survival (EFS) in newly diagnosed patients with osteosarcoma (OS).

PATIENTS AND METHODS: Six hundred seventy-seven patients with OS without clinically detectable metastatic disease were treated with one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and HDMTX and underwent definitive surgical resection of the primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 double dagger 2 factorial design. The primary end point for analysis was EFS.

RESULTS: Patients treated with the standard arm of therapy had a 3-year EFS of 71%. We could not analyze the results by factorial design because we observed an interaction between the addition of ifosfamide and the addition of MTP. The addition of MTP to standard chemotherapy achieved a 3-year EFS rate of 68%. The addition of ifosfamide to standard chemotherapy achieved a 3-year EFS rate of 61%. The addition of both ifosfamide and MTP resulted in a 3-year EFS rate of 78%.

CONCLUSION: The addition of ifosfamide in this dose schedule to standard chemotherapy did not enhance EFS. The addition of MTP to chemotherapy might improve EFS, but additional clinical and laboratory investigation will be necessary to explain the interaction between ifosfamide and MTP.

Author List

Meyers PA, Schwartz CL, Krailo M, Kleinerman ES, Betcher D, Bernstein ML, Conrad E, Ferguson W, Gebhardt M, Goorin AM, Harris MB, Healey J, Huvos A, Link M, Montebello J, Nadel H, Nieder M, Sato J, Siegal G, Weiner M, Wells R, Wold L, Womer R, Grier H

Author

Cindy L. Schwartz MD, MPH Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylmuramyl-Alanyl-Isoglutamine
Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols
Bone Neoplasms
Child
Child, Preschool
Cisplatin
Disease-Free Survival
Doxorubicin
Female
Humans
Ifosfamide
Infant
Male
Methotrexate
Osteosarcoma
Prospective Studies