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- Title
Highly effective reduced toxicity dose-intensive pilot protocol for non-metastatic limb osteogenic sarcoma (SCOS 89).
- Authors
Shkalim-Zemer, Vered; Ash, Shifra; Toledano, Helen; Kollender, Yehuda; Issakov, Josephine; Yaniv, Isaac; Cohen, Ian; Cohen, Ian J
- Abstract
<bold>Purpose: </bold>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.<bold>Methods: </bold>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/m(2)) for 2 weeks; doxorubicin (90 mg/m(2)) with dexrazoxane, combined with cisplatin (200 mg/m(2)), was added in week 3. Following methotrexate, 760 mg/m(2) 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/m(2)), and cisplatin (up to a total dose of 560 mg/m(2)). If toxicity occurred or <90 % tumor necrosis, ifosfamide (12 g/m(2)) plus etoposide (500 mg/m(2)) was substituted for doxorubicin, cisplatin, or methotrexate. Toxicity and death rates were calculated.<bold>Results: </bold>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.<bold>Conclusions: </bold>The SCOS 89 yields a high event-free survival rate with reduced nephro-/neuro-/cardiotoxicity in patients with non-metastatic limb osteosarcoma.
- Subjects
ANTINEOPLASTIC agents; BONE tumors; CISPLATIN; COMBINED modality therapy; DOXORUBICIN; ETOPOSIDE; FOLINIC acid; HEARING disorders; KIDNEY diseases; LONGITUDINAL method; MEDICAL prescriptions; METHOTREXATE; OSTEOSARCOMA; PROGNOSIS; SURVIVAL; PILOT projects; TREATMENT effectiveness; STROKE volume (Cardiac output); IFOSFAMIDE
- Publication
Cancer Chemotherapy & Pharmacology, 2015, Vol 76, Issue 5, p909
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-015-2865-x