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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)909-916
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number5
DOIs
StatePublished - 1 Nov 2015

Keywords

  • Cisplatin
  • Doxorubicin
  • Methotrexate
  • Non-metastatic limb osteosarcoma
  • Survival

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