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Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's Oncology Group. J Clin Oncol 2007 May 20;25(15):2057-62

Date

05/22/2007

Pubmed ID

17513810

DOI

10.1200/JCO.2006.07.7776

Scopus ID

2-s2.0-34249936286   78 Citations

Abstract

PURPOSE: Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma.

PATIENTS AND METHODS: From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease.

RESULTS: P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494-negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1-positive versus JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P = .61).

CONCLUSION: Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.

Author List

Schwartz CL, Gorlick R, Teot L, Krailo M, Chen Z, Goorin A, Grier HE, Bernstein ML, Meyers P, Children's Oncology Group

Author

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




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

Adolescent
Adult
Antibodies, Monoclonal
Antineoplastic Combined Chemotherapy Protocols
Bone Neoplasms
Child
Child, Preschool
Disease-Free Survival
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Female
Humans
Infant
Male
Osteosarcoma
Prospective Studies
Survival Rate
Treatment Outcome
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab