Preoperative chemotherapy for osteogenic sarcoma: Selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy

Authors

  • Gerald Rosen MD,

    Corresponding author
    1. Departments of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
    2. Departments of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
    • 1275 York Avenue, New York, NY 10021
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  • Brenda Caparros MD,

    1. Departments of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Andrew G. Huvos MD,

    1. Departments of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Cynthia Kosloff MS,

    1. Departments of Biostatistics, Nursing, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Anita Nirenberg RN, C,

    1. Departments of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
    2. Departments of Biostatistics, Nursing, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Adrienne Cacavio RN,

    1. Departments of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
    2. Departments of Biostatistics, Nursing, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Ralph C. Marcove MD,

    1. Departments of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Joseph M. Lane MD,

    1. Departments of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Bipin Mehta PHD,

    1. Departments of Laboratory of Drug Resistance, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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  • Christian Urban MD

    1. Departments of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
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Abstract

Since June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4–16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. All patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, HDMTX with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin in addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%) have remained continuously free of recurrent or metastatic disease from 6–34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6–35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival in responding patients and in helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease-free survival rate reported to date for osteogenic sarcoma.

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