Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas - Pilot study for the upcoming European rhabdomyosarcoma protocol
Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas - Pilot study for the upcoming European rhabdomyosarcoma protocol
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DOI：
10.1002/cncr.20544
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发表时间：
2004-10-01
期刊：
影响因子：
6.2
通讯作者：
Carli, M
中科院分区：
文献类型：
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作者：
Casanova, M;Ferrari, A;Carli, M
背景。继之前关于长春瑞滨治疗横纹肌肉瘤活性的报告之后，作者报告了一项初步研究的结果，该研究旨在确定长春瑞滨与连续口服低剂量环磷酰胺联合使用来治疗难治性或复发性肉瘤患者时的最佳剂量。希望在即将进行的一项涉及横纹肌肉瘤高危患者的欧洲试验中，长春瑞滨和低剂量环磷酰胺的组合可以用作维持方案。 方法。在当前的试点研究中，环磷酰胺剂量固定为每天 25 mg/m(2)，持续 28 天。长春瑞滨在第 1、8 和 15 天静脉注射，试验剂量从 15 mg/m(2) 的初始水平逐步增加到 5 mg/m(2)；不允许患者内剂量递增。结果。 2002年4月至2003年11月期间，18名2-23岁的患者在之前接受过1-4种（中位数，2种）其他治疗方案后，接受了该研究方案的治疗。总共进行了 90 个周期（中位数，每位患者 5 个周期；范围，每位患者 1-10 个周期）。在接受长春瑞滨30 mg/m2治疗的5名患者中，观察到2例剂量限制性毒性（均为4级中性粒细胞减少症）。在长春瑞滨以 25 mg/m(2) 剂量给药的 41 个周期中，15 个周期（37%）观察到 3 级中性粒细胞减少症；没有记录到与这些周期相关的其他主要毒性。在 17 名患有可测量疾病的患者中，有 1 名完全缓解，6 名部分缓解。八名可评估的横纹肌肉瘤患者中的三名（其中两例为胚胎性横纹肌肉瘤，一例为肺泡性肉瘤）对治疗有反应。结论。长春瑞滨和低剂量环磷酰胺的联合治疗被发现是可行的，并且具有抗复发性肉瘤的活性。建议在即将进行的欧洲试验中使用的维持治疗剂量为环磷酰胺 25 mg/m(2) 每天 28 天，长春瑞滨 25 mg/m(2) 第 1、8 和 15 天。(C) 2004 美国癌症协会。
BACKGROUND. Following their previous report on the activity of vinorelbine in the treatment of rhabdomyosarcoma, the authors report the results of a pilot study aimed at defining the optimal dose of vinorelbine when this agent is used in conjunction with continuous, orally administered low-dose cyclophosphamide to treat patients with refractory or recurrent sarcoma. It is hoped that the combination of vinorelbine and low-dose cyclophosphamide can be used as a maintenance regimen in an upcoming European trial involving high-risk patients with rhabdomyosarcoma.METHODS. in the current pilot study, the cyclophosphamide dose was fixed at 25 mg/m(2) per day for 28 days. Vinorelbine was administered intravenously on Days 1, 8, and 15, with trial doses escalated from an initial level of 15 mg/m(2) in steps of 5 mg/m(2); intrapatient dose escalation was not allowed.RESULTS. Between April 2002 and November 2003, 18 patients ages 2-23 years were treated with the study regimen after having received 1-4 (median, 2) other regimens previously. Ninety cycles were administered in total (median, 5 cycles per patient; range, 1-10 cycles per patient). Two cases of dose-limiting toxicity (Grade 4 neutropenia in both cases) were observed among the 5 patients who received vinorelbine at a dose of 30 mg/m(2). Of the 41 cycles in which vinorelbine was administered at a dose of 25 mg/m(2), Grade 3 neutropenia was observed in 15 (37%); no other major toxicity was documented in association with these cycles. One complete remission and 6 partial remissions were noted among the 17 patients who had measurable disease. Three of the eight assessable patients with rhabdomyosarcoma (which was embryonal in two cases and alveolar in one) had responses to treatment.CONCLUSIONS. Combination therapy involving vinorelbine and low-dose cyclo-phosphamide was found to be feasible and to possess activity against recurrent sarcomas. The maintenance therapy doses recommended for use in the upcoming European trial are cyclophosphamide 25 mg/m(2) per day for 28 days and vinorelbine 25 mg/m(2) on Days 1, 8, and 15. (C) 2004 American Cancer Society.