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Multiple Drug Resistance in Osteogenic Sarcoma: INT0133 From the Children's Oncology Group

Cindy L. Schwartz, Richard Gorlick, Lisa Teot, Mark Krailo, Zhengjia Chen, Allen Goorin, Holcombe E. Grier, Mark L. Bernstein, Paul Meyers

From the Hasbro Children's Hospital/Brown Medical School, Providence, RI; Montefiore Medical Center, Bronx; Memorial Sloan Kettering Cancer Center, New York, NY; Children's Hospital of Pittsburgh, Pittsburgh, PA; Keck School of Medicine, University of Southern California, Los Angeles; Children's Oncology Group Operations Center, Arcadia, CA; Dana-Farber Cancer Institute and Children's Hospital, Boston, MA; and Hôpital Sainte-Justine Montreal, Quebec, Canada

Address reprint requests to Cindy L. Schwartz, MD, Hasbro Children's Hospital/Brown Medical School, 593 Eddy St MP117, Providence, RI 02903; e-mail: cschwartz1{at}lifespan.org

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.

Supported by Grants No. U10 CA 98543, CA 30969, and CA 13539 from the National Institutes of Health/National Cancer Institute. A complete listing of grant support for research conducted by Children's Cancer Group and Pediatric Oncology Group before initiation of the Children's Oncology Group grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm.

Presented in part at the 36th Annual Meeting of the American Society of Clinical Oncology, May 20-23, 2000, New Orleans, LA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Correspondence

• Prognostic Value of P-Glycoprotein in High-Grade Osteosarcoma
  Massimo Serra, Piero Picci, Stefano Ferrari, and Gaetano Bacci
  JCO 2007 25: 4858-4860 [Full Text]

This article has been cited by other articles:

				M. Serra, P. Picci, S. Ferrari, and G. Bacci Prognostic Value of P-Glycoprotein in High-Grade Osteosarcoma J. Clin. Oncol., October 20, 2007; 25(30): 4858 - 4860. [Full Text] [PDF]

				C. L. Schwartz, R. Gorlick, L. Teot, M. Krailo, A. Goorin, H. E. Grier, M. L. Bernstein, and P. Meyers In Reply J. Clin. Oncol., October 20, 2007; 25(30): 4860 - 4861. [Full Text] [PDF]