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

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.