Bone Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Bone Cancer, including details on symptoms, types, treatment.

Upfront window trial of topotecan in previously untreated children and adolescents with poor prognosis metastatic osteosarcoma: children's Cancer Group (CCG) 7943.

Seibel NL, Krailo M, Chen Z, Healey J, Breitfeld PP, Drachtman R, Greffe B, Nachman J, Nadel H, Sato JK, Meyers PA, Reaman GH

Hematology-Oncology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC 20010, USA. nseibel@cnmc.org

BACKGROUND: Patients with metastatic osteosarcoma have a poor prognosis. The objectives of the study were to determine the antitumor activity and toxicity of topotecan (daily x5) in newly diagnosed patients with metastatic osteosarcoma followed by chemotherapy (ifosfamide, carboplatin, etoposide [ICE], alternating with cisplatin and doxorubicin [CD]). METHODS: Newly diagnosed patients (< or =30 years of age) with extensive metastatic disease (primary and > or =5 pulmonary nodules and/or bone metastases) with normal hepatic, renal, and cardiac function were eligible. Patients were eligible to receive further topotecan after standard chemotherapy if they exhibited a response. Twenty-eight patients were enrolled. Seventeen had metastases to the lung only and 11 had metastases to the bone or multiple sites. Of 28 patients enrolled, 27 could be evaluated for response. A limited dose escalation was incorporated. RESULTS: No responses were seen in the 11 patients treated at 3 mg/m(2)/day. One partial response (PR) and 1 clinical response (CLR) were reported among 15 patients who received topotecan at 3.5 mg/m(2)/day. No dose-limiting toxicity was observed. Principal nondose-limiting toxicities were hematologic and gastrointestinal. The 2- and 5-year event-free survival rates were low, 7% and 4%, respectively, but the 2- and 5-year overall survival rates were 44% and 22%, respectively. CONCLUSIONS: Topotecan at dose of 3.5 mg/m(2)/day can be safely administered upfront to newly diagnosed patients without excessive toxicity. Insufficient activity was seen with topotecan in this schedule to warrant further studies in osteosarcoma. The combination of ICE and CD was tolerable when delivered after initial topotecan therapy.

Published 14 May 2007 in Cancer, 109(8): 1646-53.
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