Seibel Nita L, Krailo Mark, Chen Zhengjia, Healey John, Breitfeld Philip P, Drachtman Richard, Greffe Brian, Nachman James, Nadel Helen, Sato Judith K, Meyers Paul A, Reaman Gregory H
Hematology-Oncology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC 20010, USA.
Cancer. 2007 Apr 15;109(8):1646-53. doi: 10.1002/cncr.22553.
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]).
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.
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.
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.
转移性骨肉瘤患者预后较差。本研究的目的是确定拓扑替康（每日×5）对新诊断的转移性骨肉瘤患者的抗肿瘤活性和毒性，随后进行化疗（异环磷酰胺、卡铂、依托泊苷[ICE]，与顺铂和多柔比星交替使用[CD]）。
符合条件的患者为新诊断的（年龄≤30岁）、患有广泛转移性疾病（原发性且≥5个肺结节和/或骨转移）、肝、肾和心功能正常的患者。如果患者在标准化疗后有反应，则有资格接受进一步的拓扑替康治疗。共纳入28例患者。17例仅发生肺转移，11例发生骨转移或多部位转移。在纳入的28例患者中，27例可评估反应情况。采用了有限的剂量递增方案。
11例接受3mg/m²/天治疗的患者未出现反应。15例接受3.5mg/m²/天拓扑替康治疗的患者中，报告了1例部分缓解（PR）和1例临床缓解（CLR）。未观察到剂量限制性毒性。主要的非剂量限制性毒性为血液学和胃肠道毒性。2年和5年无事件生存率较低，分别为7%和4%，但2年和5年总生存率分别为44%和22%。
3.5mg/m²/天剂量的拓扑替康可安全地预先给予新诊断的患者，且无过度毒性。在此方案中，拓扑替康的活性不足，不值得在骨肉瘤中进一步研究。初始拓扑替康治疗后给予ICE和CD联合方案是可耐受的。
