Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: Results from phase I/II studies
Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: Results from phase I/II studies
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DOI：
10.1200/jco.2004.11.120
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发表时间：
2004-05-15
影响因子：
45.3
通讯作者：
Curley, SA
中科院分区：
文献类型：
--
作者：
Izzo, F;Marra, P;Curley, SA
目的最近，我们报道大量人肝细胞癌（HCC）细胞系精氨酸营养缺陷。在此，我们报告了使用与聚乙二醇缀合的氨基酸降解酶精氨酸脱亚胺酶 (ADI) (ADI-SS PEG 20,000 mw) 作为降低血浆精氨酸治疗 HCC 的方法所获得的结果。该研究是一项队列剂量递增 I/II 期研究。患者和方法药效学研究表明，160 U/m(2) 的 ADI-SS PEG 20,000 mw 剂量水平足以将血浆精氨酸从约 130 mumol/L 的静息水平降低至低于检测水平 (< 2 mumol/L)，持续时间超过 7 天，该剂量后来定义为最佳剂量 生物剂量。所有患者均以最佳生物剂量接受三个周期。结果即使对于连续 3 个月治疗期间未检测到血浆精氨酸的患者，该疗法也具有良好的耐受性。在入组的 19 名患者中，两名患者完全缓解，七名患者部分缓解，七名患者疾病稳定，三名患者疾病进展。参加本研究的 19 名患者的中位生存期为 410 天，其中 4 名患者目前仍存活（> 680 天）。结论 HCC 患者消除所有可检测到的血浆精氨酸耐受性良好，并且对某些 HCC 患者的治疗似乎有效。有必要在更多患有 HCC 以及精氨酸营养缺陷型人类肿瘤的个体中进一步测试 ADI-SS PEG 20,000 mw。 (C) 2004 年，美国临床肿瘤学会。
PurposeRecently, we reported that a large number of human hepatocellular cancer (HCC) cell lines were auxotrophic for arginine. Here we report the results obtained with the amino acid-degrading enzyme arginine deiminase (ADI) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma arginine to treat HCC. The study was a cohort dose-escalation phase I/II study.Patients and MethodsPharmacodynamic studies indicated an ADI-SS PEG 20,000 mw dose level of 160 U/m(2) was sufficient to lower plasma arginine from a resting level of approximately 130 mumol/L to below the level of detection ( < 2 mumol/L) for more than 7 days, a dose later defined as the optimal biologic dose. All patients were to receive three cycles at the optimum biologic dose.ResultsThis therapy was well tolerated, even in patients who had no detectable plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled, two had a complete response, seven had a partial response, seven had stable disease, and three had progressive disease. The median survival for the 19 patients enrolled on this study was 410 days, with four patients still alive at present ( > 680 days).ConclusionElimination of all detectable plasma arginine in patients with HCC was well tolerated and seemed to be effective in the treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with HCC as well as other human tumors auxotrophic for arginine is warranted. (C) 2004 by American Society of Clinical Oncology.