TY - JOUR
T1 - Multiple drug resistance in osteogenic sarcoma
T2 - INT0133 from the Children's Oncology Group
AU - Schwartz, Cindy L
AU - Gorlick, Richard
AU - Teot, Lisa
AU - Krailo, Mark
AU - Chen, Zhengjia
AU - Goorin, Allen
AU - Grier, Holcombe E.
AU - Bernstein, Mark L.
AU - Meyers, Paul
PY - 2007/5/20
Y1 - 2007/5/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2006.07.7776
DO - 10.1200/JCO.2006.07.7776
M3 - Article
C2 - 17513810
AN - SCOPUS:34249936286
SN - 0732-183X
VL - 25
SP - 2057
EP - 2062
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -