晚期实体癌患者对不含聚氧乙烯蓖麻油注射用紫杉醇白蛋白纳米粒悬浮液的临床耐受性研究

A Tolerability Study of A Cremophor-free Albumin Bound Nanoparticle Paclitaxel Intravenously Administered in Patients with Advanced Solid Tumor

背景与目的:不含聚氧乙烯蓖麻油注射用紫杉醇白蛋白纳米粒悬浮液(中国商品名:凯素)是美国生物科学公司(AmericanBioSceince,Inc.)研制的全新的紫杉醇制剂。本文目的旨在评价其在国内患者的临床耐受性,建立该药在国内患者的最大耐受剂量,并为下一阶段临床研究的推荐剂量提供临床依据。方法:剂量递增Ⅰ期临床试验,剂量范围为135～350mg/m2,每一剂量组至少有3例患者。凯素静脉滴注30min,每3周重复一疗程。每疗程用药前不给予患者抗过敏预治疗。结果:22例患者接受了至少一个疗程的治疗,共完成94个疗程。患者能较好地耐受凯素治疗,整个治疗过程未发现严重过敏反应;绝大部分(95%)AEs为CTC1度或2度,3度或以上仅占5%。骨髓抑制导致外周血白细胞减少及外周感觉神经毒性是最常见的毒性反应,但程度均较轻。4度ANC减少仅1次报告,整个研究过程无患者需要G-CSF支持。剂量限制性毒性见于350mg/m2剂量组,表现为1例患者出现4度ANC减少及1例患者出现3度复视/视物模糊,但症状均在短时间内恢复正常。凯素在国内患者的MTD为300mg/m2。在21例可评价疗效的患者中,CR1例,PR7例,SD9例,PD4例,总有效率(CR+PR)为38%。结论:Ⅰ期临床研究显示凯素具有不需使用预治疗,滴注时间短,较高的紫杉醇MTD及毒性较低的临床特点。

BACKGROUND &OBJECTIVE: Capxol is a Cremophor-free,protein stabi li zed,nanoparticle formulation of paclitaxel. This phase Ⅰstudy was designed to e valuate the tolerability/safety,toxicity profile,and maximum tolerated dose (MTD ) of Capxol administered intravenously in Chinese patients with advanced solid t umor,and to provide the recommending dose for the phase Ⅱtrial. METHOD: Capxol was administered intravenously over 30 minutes,no premedication was required. Do ses of Capxol ranged from 135 to 350 mg/m2. The treatment was repeated at 3 week s interval. RESULTS: 22 patients were treated with Capxol and totally 94 treatme nts cycles were completed. No acute hypersensitivity reactions were observed dur ing the infusion period. The treatment was tolerated well. Most of AEs (95%) we re grade 1/2; ≥grade 3 AEs were only 5%. The most common toxicities were mild leucopenia and peripheral sensory neuropathy. The dose-limiting toxicities,whic h occurred at dose level of 350 mg/m2,were grade 4 neutropenia (1 out of 3 patie nts) and grade 3 diplopia (1 out of 3 patients). The MTD was thus determined at 300 mg/m2. Among 21 patients who were evaluable for efficacy,1 CR,7 PR,9 SD,4 PD were observed,overall response rate (CR+PR) was 38%. CONCLUSION: This phase Ⅰtrial has demonstrated that Capxol has several advantages on clinical applicat ion,which include non-premedication required,shorter infusion time,higher pacli taxel MTD and safer toxicity. The results support for that a phase Ⅱclinical tr ial to further evaluate the antitumor activity of this drug in Chinese patients is worthy. The recommended dose for phase Ⅱclinical trial is 260 mg/m2,I.V. ove r 30 minutes,and treatment repeats at every 3 weeks.