TY - JOUR
T1 - Highly effective reduced toxicity dose-intensive pilot protocol for non-metastatic limb osteogenic sarcoma (SCOS 89)
AU - Shkalim-Zemer, Vered
AU - Ash, Shifra
AU - Toledano, Helen
AU - Kollender, Yehuda
AU - Issakov, Josephine
AU - Yaniv, Isaac
AU - Cohen, Ian J.
N1 - Publisher Copyright:
© 2015 Springer-Verlag Berlin Heidelberg.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
KW - Cisplatin
KW - Doxorubicin
KW - Methotrexate
KW - Non-metastatic limb osteosarcoma
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84945465388&partnerID=8YFLogxK
U2 - 10.1007/s00280-015-2865-x
DO - 10.1007/s00280-015-2865-x
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AN - SCOPUS:84945465388
SN - 0344-5704
VL - 76
SP - 909
EP - 916
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 5
ER -