Phase II study of phenylacetate in patients with recurrent malignant glioma: A North American brain tumor consortium report
Phase II study of phenylacetate in patients with recurrent malignant glioma: A North American brain tumor consortium report
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DOI：
10.1200/jco.1999.17.3.984
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发表时间：
1999-03-01
影响因子：
45.3
通讯作者：
Prados, MD
中科院分区：
文献类型：
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作者：
Chang, SM;Kuhn, JG;Prados, MD
目的：测定苯乙酸乙酯对复发恶性胶质瘤患者的有效率、治疗失败时间和毒性，并确定多次持续滴注苯乙酸乙酯后的血药浓度。计划包括2周的持续静脉输液，然后是2周的休息时间(14天开始，14天休息)。最初使用的苯乙酸酯起始量为每天400毫克/公斤总体重，随后根据理想体重改为400毫克/公斤/天。允许患者内剂量增加到最大450毫克/公斤理想体重/天。每8周评估一次肿瘤反应。使用美国国家癌症研究所的一般毒性标准来评估毒性。检测患者在前两次14天输液中的血药浓度。结果：从1994年12月到1996年12月共纳入43名患者。在这些患者中，有40名患者的毒性和治疗反应可以评估。主要的毒性反应是可逆性的疲倦和嗜睡症状，只有轻微的血液毒性。在40名患者中，30名(75%)在2个月内治疗失败，7名(17.5%)病情稳定，3名(7.5%)有反应，定义为肿瘤减少50%以上，治疗失败的中位时间为2个月。已有35名患者死亡，中位生存期为8个月。药代动力学数据显示，苯乙酸酯在1周和2周、5周和6周的平均血药浓度无差异。结论：在此剂量方案下，苯乙酸酯对复发性恶性胶质瘤患者几乎没有活性。对这种药物的进一步研究需要对不同的剂量计划进行评估。1999年由美国临床肿瘤学学会评选。
Purpose: To determine the response rate, time to treatment failure, and toxicity of phenylacetate in patients with recurrent malignant glioma and to identify plasma concentrations achieved during repeated continuous infusion of this agent.Patients and Methods: Adult patients with recurrent malignant glioma were treated with phenylacetate. The schedule consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off). A starting dose of 400 mg/kg total body weight per day of phenylacetate was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer institute common toxicity criteria were used to assess toxicity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed.Results: Forty-three patients were enrolled between December 1994 and December 1996. Of these, 40 patients were assessable for toxicity and response to therapy. Reversible symptoms of fatigue and somnolence were the primary toxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2 months, seven (17.5%) had stable disease, and three (7.5%) had a response defined as more than 50% reduction in the tumor Median time to treatment failure was 2 months. Thirty five patients have died, with a median survival of 8 months. Pharmacokinetic data for this dose schedule showed no difference in the mean plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5 and 6.Conclusion: phenylacetate has little activity at this dose schedule in patients with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule. a 1999 by American Society of Clinical Oncology.