Chang S M, Kuhn J G, Robins H I, Schold S C, Spence A M, Berger M S, Mehta M P, Bozik M E, Pollack I, Schiff D, Gilbert M, Rankin C, Prados M D
University of California Medical Center, San Francisco, USA.
J Clin Oncol. 1999 Mar;17(3):984-90. doi: 10.1200/JCO.1999.17.3.984.
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.
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.
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.
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.
确定苯乙酸酯对复发性恶性胶质瘤患者的缓解率、治疗失败时间及毒性，并确定在重复持续输注该药物期间达到的血浆浓度。
成年复发性恶性胶质瘤患者接受苯乙酸酯治疗。治疗方案为持续2周的静脉输注，随后休息2周（用药14天，停药14天）。初始起始剂量为每天400mg/kg总体重的苯乙酸酯，随后根据理想体重改为400mg/kg/d。允许患者个体剂量递增至最大450mg/kg理想体重/d。每8周评估肿瘤反应。采用美国国立癌症研究所通用毒性标准评估毒性。评估患者前两个14天输注期间达到的血浆浓度。
1994年12月至1996年12月期间纳入43例患者。其中，40例患者可评估毒性及对治疗的反应。疲劳和嗜睡的可逆症状是主要毒性，仅有轻度血液学毒性。40例患者中有30例（75%）在2个月内治疗失败，7例（17.5%）疾病稳定，3例（7.5%）有反应，定义为肿瘤缩小超过50%。治疗失败的中位时间为2个月。35例患者死亡，中位生存期为8个月。该剂量方案的药代动力学数据显示，第1周和第2周之间或第5周和第6周之间苯乙酸酯的平均血浆浓度无差异。
在此剂量方案下，苯乙酸酯对复发性恶性胶质瘤患者几乎无活性。对该药物的进一步研究需要评估不同的剂量方案。
