A Phase 2 Trial of Glufosfamide in Combination With Gemcitabine in Chemotherapy-Naive Pancreatic Adenocarcinoma
A Phase 2 Trial of Glufosfamide in Combination With Gemcitabine in Chemotherapy-Naive Pancreatic Adenocarcinoma
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DOI：
10.1097/coc.0b013e3181979204
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发表时间：
2010-04-01
影响因子：
2.6
通讯作者：
Loehrer, Patrick J.
中科院分区：
文献类型：
--
作者：
Chiorean, Elena G.;Dragovich, Tomislav;Loehrer, Patrick J.
目的：一项葡膦酰胺加吉西他滨的剂量递增研究表明，该联合用药可以安全地以全剂量给药。本II期研究的目的是评估这种组合在化疗初治的胰腺腺癌的安全性和有效性。方法：符合条件的患者有转移性和/或局部晚期胰腺癌，Karnofsky体力状态>= 70，肌酐清除率（CrCL）>= 60 mL/min，和可接受的器官功能。患者在每28天为一周期的第1天接受静脉注射葡膦酰胺4500 mg/m2，在第1、8和15天接受静脉注射吉西他滨1000 mg/m2。主要终点是反应率。结果：29例患者入组，14例男性，中位年龄58岁。23例（79%）患者有远处转移。中位治疗周期为4（范围：1-18+）。在28例患者中，5例（18%; 95% CI：6%-37%）患者确认部分缓解（中位持续时间：8.4个月），1例患者未确认部分缓解。11名患者（39%）病情稳定。中位无进展生存期为3.7个月，中位总生存期为6个月，1年生存率为32%。23例（79%）患者发生34级中性粒细胞减少，10例（34%）患者发生34级血小板减少。27例患者中有10例（37%）的CrCL低于60 mL/min。肾功能衰竭4例。CrCL的减少与glufosfamide和异磷酰胺芥药代动力学曲线下面积相关。结论：glufosfamide加吉西他滨的组合在胰腺癌中是活跃的，但是，血液学和肾脏毒性明显。应探索葡环磷酰胺+吉西他滨的替代给药。
Objectives: A dose-escalation study of glufosfamide plus gemcitabine showed that the combination could be administered safely at full doses. The purpose of this phase II study was to evaluate the safety and efficacy of this combination in chemotherapy-naive pancreatic adenocarcinoma.Methods: Eligible patients had metastatic and/or locally advanced pancreatic adenocarcinoma, Karnofsky performance status >= 70, creatinine clearance (CrCL) >= 60 mL/min, and acceptable organ function. Patients received glufosfamide 4500 mg/m(2) intravenous on day 1 and gemcitabine 1000 mg/m2 intravenous on Days 1, 8, and 15 of every 28-day cycle. The primary end point was response rate.Results: Twenty-nine patients were enrolled; 14 male, median age 58 years. Twenty-three (79%) patients had distant metastases. Median cycles on treatment was 4 (range: 1-18+). Of 28, 5 (18%; 95% CI: 6%-37%) patients had a confirmed partial response (median duration: 8.4 months) and 1 had an unconfirmed partial response. Eleven patients (39%) had stable disease. Median progression-free survival was 3.7 months, median overall survival was 6 months, and 1-year survival was 32%. Grade 3/4 neutropenia occurred in 23 (79%) patients and grade 3/4 thrombocytopenia in 10 (34%) patients. The CrCL fell below 60 mL/min in 10 of 27 (37%) patients. Renal failure occurred in 4 patients. Decrease in CrCL was correlated with glufosfamide and isophosphoramide mustard pharmacokinetic area under the curve.Conclusions: The combination of glufosfamide plus gemcitabine is active in pancreatic cancer; however, hematologic and renal toxicity were pronounced. Alternative dosing of glufosfamide plus gemcitabine should be explored.