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Highly effective reduced toxicity dose-intensive pilot protocol for non-metastatic limb osteogenic sarcoma (SCOS 89)

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Abstract

Purpose

Aggressive chemotherapy protocols for non-metastatic limb osteosarcoma have improved histological response without affecting prognosis. This study evaluated the toxicity and outcome of a dose-intensive, high-dose 3- to 5-drug pilot protocol, SCOS 89.

Methods

The cohort included 26 patients (14 male; ages 6.5–22 years) with non-metastatic limb osteosarcoma treated at a tertiary pediatric medical center between 1989 and 2013. Preoperatively, patients received two courses of once-weekly pulses of high-dose methotrexate (12–30 g/m2) for 2 weeks; doxorubicin (90 mg/m2) with dexrazoxane, combined with cisplatin (200 mg/m2), was added in week 3. Following methotrexate, 760 mg/m2 of folinic acid was administered. Postoperative chemotherapy was continued to a total of 14 courses of methotrexate, doxorubicin (up to a total dose of 360 mg/m2), and cisplatin (up to a total dose of 560 mg/m2). If toxicity occurred or <90 % tumor necrosis, ifosfamide (12 g/m2) plus etoposide (500 mg/m2) was substituted for doxorubicin, cisplatin, or methotrexate. Toxicity and death rates were calculated.

Results

All patients underwent definitive limb salvage surgery. Six patients died of infection, recurrent disease, or secondary malignancy. Median follow-up was 100 months (range 2–290). Event-free and overall survival rates, respectively, were 88 and 96 % at 2 years, 80 and 87.6 % at 5 years, 80 and 78 % at 10 years. Eleven patients required ifosfamide/etoposide substitution. One patient had a transient decreased left ventricular ejection fraction. Two patients developed acute nephrotoxicity during therapy, but no neurotoxicity. Seven patients had hearing impairment.

Conclusions

The SCOS 89 yields a high event-free survival rate with reduced nephro-/neuro-/cardiotoxicity in patients with non-metastatic limb osteosarcoma.

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Authors and Affiliations

  1. Department of Pediatric Hematology-Oncology, Schneider Children’s Medical Center of Israel, 49202, Petach Tikva, Israel

    Vered Shkalim-Zemer, Shifra Ash, Helen Toledano, Isaac Yaniv & Ian J. Cohen

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Vered Shkalim-Zemer, Shifra Ash, Helen Toledano, Yehuda Kollender, Josephine Issakov, Isaac Yaniv & Ian J. Cohen

  3. Unit of Orthopedic Oncology, Institute of Pathology, Sourasky Medical Center, Tel Aviv, Israel

    Yehuda Kollender

  4. Unit of Bone and Soft Tissue Tumors, Institute of Pathology, Sourasky Medical Center, Tel Aviv, Israel

    Josephine Issakov

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  1. Vered Shkalim-Zemer
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Correspondence to Ian J. Cohen.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional local ethics committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Shkalim-Zemer, V., Ash, S., Toledano, H. et al. Highly effective reduced toxicity dose-intensive pilot protocol for non-metastatic limb osteogenic sarcoma (SCOS 89). Cancer Chemother Pharmacol 76, 909–916 (2015). https://doi.org/10.1007/s00280-015-2865-x

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  • DOI: https://doi.org/10.1007/s00280-015-2865-x

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