盐酸苯达莫司汀治疗难治性软组织肉瘤患者：德国肉瘤协作组（AIO-001）的一项非对照多中心2期研究

Bendamustine hydrochloride in patients with refractory soft tissue sarcoma: a noncomparative multicenter phase 2 study of the German sarcoma group (AIO-001).

作者信息

Hartmann Joerg T, Mayer Frank, Schleicher Jan, Horger Marius, Huober Jens, Meisinger Ines, Pintoffl Jan, Käfer Gabriele, Kanz Lothar, Grünwald Viktor

机构信息

Department of Medical Oncology, Hematology, Immunology, Rheumatology, and Pulmonology, Medical Center, Eberhard-Karls-University, Tuebingen, Germany.

出版信息

Cancer. 2007 Aug 15;110(4):861-6. doi: 10.1002/cncr.22846.

DOI:10.1002/cncr.22846

PMID:17599772

Abstract

BACKGROUND

For patients with advanced soft tissue sarcoma (STS), no standard treatment is established after previous chemotherapy with anthracyclines and ifosfamide. Bendamustine hydrochloride is a bifunctional alkylating agent that is not cross-resistant to other DNA-interacting substances including anthracyclines and oxazaphosphorines. It has shown single-agent activity in refractory lymphoma, myeloma, and some solid tumors. A phase 2 study was initiated to evaluate the efficacy of bendamustine in previously treated patients.

METHODS

Thirty-six of 44 screened patients were included and received a total of 101 cycles (median, 2 cycles; range, 1-8 cycles), 21 as second-line treatment and 15 as third-line treatment. The median age was 55 years (range, 18-79 years). Bendamustine was given as an intravenous infusion over 30 minutes at a dose of 100 mg/m(2) on 2 consecutive days and repeated every 28 days. Eighty-eight percent of cycles could be given without dose or schedule modification.

RESULTS

The toxicity profile was mild, consisting of National Cancer Institute Common Toxicity Criteria (CTC) grade 3 neutropenia in 11% and grade 3 anemia in 9% of patients. Nonhematologic toxicities were noticed with CTC grade 3 fever in 3% of patients. No other grade 3 toxicity and no treatment-related toxic deaths were observed. The best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 1 partial remission (3%) and disease stabilizations in 31% of patients. Six of 15 patients (40%) with leiomyosarcoma histology achieved stable disease. The estimated 3-month and 6-month progression-free survival rates were 35.3% and 23.5%, respectively, for all histologic subtypes included.

CONCLUSIONS

In patients with refractory STS, bendamustine is well tolerated and appears moderately effective, particularly in patients with leiomyosarcoma histology.

摘要

背景

对于晚期软组织肉瘤（STS）患者，在先前接受蒽环类药物和异环磷酰胺化疗后，尚无标准治疗方案。盐酸苯达莫司汀是一种双功能烷化剂，与包括蒽环类药物和氮杂膦类药物在内的其他与DNA相互作用的物质不存在交叉耐药性。它在难治性淋巴瘤、骨髓瘤和一些实体瘤中显示出单药活性。开展了一项2期研究以评估苯达莫司汀对先前接受过治疗的患者的疗效。

方法

44例筛选患者中的36例被纳入研究，共接受了101个周期（中位数为2个周期；范围为1 - 8个周期）的治疗，其中21例为二线治疗，15例为三线治疗。中位年龄为55岁（范围为18 - 79岁）。苯达莫司汀以100 mg/m²的剂量连续2天静脉输注30分钟，每28天重复一次。88%的周期可以在不调整剂量或给药方案的情况下进行。

结果

毒性反应较轻，11%的患者出现美国国立癌症研究所通用毒性标准（CTC）3级中性粒细胞减少，9%的患者出现3级贫血。3%的患者出现CTC 3级发热等非血液学毒性。未观察到其他3级毒性反应和与治疗相关的毒性死亡。根据实体瘤疗效评价标准（RECIST），最佳总体缓解为1例部分缓解（3%），31%的患者病情稳定。15例平滑肌肉瘤组织学类型的患者中有6例（40%）病情稳定。所有组织学亚型的估计3个月和6个月无进展生存率分别为35.3%和23.5%。