Frontline treatment of localized osteosarcoma without methotrexate

Results of the St. Jude Children's Research Hospital OS99 Trial

Authors

  • Najat C. Daw MD,

    Corresponding author
    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
    Current affiliation:
    1. Children's National Medical Center-Main Hospital, Washington, DC
    • Division of Pediatrics, Unit 87, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009

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    • Fax: (713) 792-0608

  • Michael D. Neel MD,

    1. Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Bhaskar N. Rao MD,

    1. Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Catherine A. Billups MS,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Jianrong Wu PhD,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Jesse J. Jenkins MD,

    1. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Juan Quintana MD,

    1. Department of Pediatrics, Luis Calvo MacKenna Hospital and the Chilean National Pediatric Oncology Group (PINDA), Santiago, Chile
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  • Lori Luchtman-Jones MD,

    1. Division of Pediatric Hematology/Oncology, Washington University Medical School, St. Louis, Missouri
    Current affiliation:
    1. Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX
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  • Milena Villarroel MD,

    1. Department of Pediatrics, Luis Calvo MacKenna Hospital and the Chilean National Pediatric Oncology Group (PINDA), Santiago, Chile
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  • Victor M. Santana MD

    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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  • We are indebted to Berlex Laboratories (Seattle, Wash) for providing granulocyte-macrophage–colony-stimulating factor (GM-CSF) for Chilean patients and to Wright Medical Company (Arlington, Tenn) for providing prostheses at a reduced price for Chilean patients. We acknowledge the valuable contributions of Charles B. Pratt, MD (deceased); Fredric A. Hoffer, MD; Carlos Rodriguez-Galindo, MD; Gaston K. Rivera, MD; Karen Wodowski, PNP; Vickie Given, RN; Dana Hawkins, RN, BSN, CCRC; Valerie McPherson, CCRP; and Debbie Poe, CCRP (St. Jude) and of Myriam Campbell, MD; Juan Jose Latorre, MD; Jesus Ortega, MD; and Emma Concha, MD (Chile). We thank Sharon Naron for editorial assistance. We thank Christine Wogan for her substantive editing of the manuscript.

Abstract

BACKGROUND:

The standard treatment of osteosarcoma includes cisplatin and high-dose methotrexate (HDMTX); both agents exert significant toxicity, and HDMTX requires complex pharmacokinetic monitoring and leucovorin rescue. In the previous OS91 trial, the treatment of localized disease with carboplatin, ifosfamide, doxorubicin, and HDMTX yielded outcomes comparable to those of cisplatin-based regimens and caused less toxicity. To build on this experience, the authors conducted a multi-institutional trial (OS99) that evaluated the efficacy of carboplatin, ifosfamide, and doxorubicin without HDMTX in patients with newly diagnosed, localized, resectable osteosarcoma.

METHODS:

Treatment was comprised of 12 cycles of chemotherapy administered over 35 weeks: 3 cycles of carboplatin (dose targeted to area under the concentration-time curve of 8 mg/mL × min on Day 1) and ifosfamide (at a dose of 2.65 g/m2 daily ×3 days) and 1 cycle of doxorubicin (at a dose of 25 mg/m2 daily ×3 days) before surgical resection, followed by 2 additional cycles of the combination of carboplatin and ifosfamide and 3 cycles each of doxorubicin (25 mg/m2 daily ×2 days) combined with ifosfamide or carboplatin.

RESULTS:

A total of 72 eligible patients (median age, 13.4 years) were enrolled between May 1999 and May 2006. Forty of the 66 (60.6%) evaluable patients had good histologic responses (>90% tumor necrosis) to preoperative chemotherapy. The estimated 5-year event-free survival rate was 66.7% ± 7.0% for the OS99 trial compared with 66.0% ± 6.8% for the OS91 trial (P = .98). The estimated 5-year survival rate was 78.9% ± 6.3% for the OS99 trial and 74.5% ± 6.3% for the OS91 trial (P = .40).

CONCLUSIONS:

The regimen used in the OS99 trial was found to produce outcomes comparable to those of cisplatin-containing or HDMTX-containing regimens. This therapy offers a good alternative for patients, particularly those who demonstrate an intolerance of HDMTX, and for institutions that cannot provide pharmacokinetic monitoring for MTX. Cancer 2011. © 2011 American Cancer Society.

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