Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's Oncology Group.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Schwartz
Cindy L
CL
Hasbro Children's Hospital/Brown Medical School, Providence, RI 02903, USA. cschwartz1@lifespan.org
Gorlick
Richard
R
Teot
Lisa
L
Krailo
Mark
M
Chen
Zhengjia
Z
Goorin
Allen
A
Grier
Holcombe E
HE
Bernstein
Mark L
ML
Meyers
Paul
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy*; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal