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Highly effective reduced toxicity dose-intensive pilot protocol for non-metastatic limb osteogenic sarcoma (SCOS 89).
Cancer Chemother Pharmacol 2015; 76(5):909-16CC

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/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.

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.

Authors+Show Affiliations

Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, 49202, Petach Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, 49202, Petach Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, 49202, Petach Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Unit of Orthopedic Oncology, Institute of Pathology, Sourasky Medical Center, Tel Aviv, Israel.Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Unit of Bone and Soft Tissue Tumors, Institute of Pathology, Sourasky Medical Center, Tel Aviv, Israel.Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, 49202, Petach Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, 49202, Petach Tikva, Israel. icohen@tau.ac.il. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. icohen@tau.ac.il.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26365289

Citation

Shkalim-Zemer, Vered, et al. "Highly Effective Reduced Toxicity Dose-intensive Pilot Protocol for Non-metastatic Limb Osteogenic Sarcoma (SCOS 89)." Cancer Chemotherapy and Pharmacology, vol. 76, no. 5, 2015, pp. 909-16.
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. 2015;76(5):909-16.
Shkalim-Zemer, V., Ash, S., Toledano, H., Kollender, Y., Issakov, J., Yaniv, I., & Cohen, I. J. (2015). Highly effective reduced toxicity dose-intensive pilot protocol for non-metastatic limb osteogenic sarcoma (SCOS 89). Cancer Chemotherapy and Pharmacology, 76(5), pp. 909-16. doi:10.1007/s00280-015-2865-x.
Shkalim-Zemer V, et al. Highly Effective Reduced Toxicity Dose-intensive Pilot Protocol for Non-metastatic Limb Osteogenic Sarcoma (SCOS 89). Cancer Chemother Pharmacol. 2015;76(5):909-16. PubMed PMID: 26365289.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2015/09/13/ PY - 2015/07/18/received PY - 2015/09/02/accepted PY - 2015/9/15/entrez PY - 2015/9/15/pubmed PY - 2016/1/29/medline KW - Cisplatin KW - Doxorubicin KW - Methotrexate KW - Non-metastatic limb osteosarcoma KW - Survival SP - 909 EP - 16 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother. Pharmacol. VL - 76 IS - 5 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/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. 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. SN - 1432-0843 UR - https://www.unboundmedicine.com/medline/citation/26365289/Highly_effective_reduced_toxicity_dose_intensive_pilot_protocol_for_non_metastatic_limb_osteogenic_sarcoma__SCOS_89__ L2 - https://dx.doi.org/10.1007/s00280-015-2865-x DB - PRIME DP - Unbound Medicine ER -