Department of Internal Medicine, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Jpn J Clin Oncol. 2010 May;40(5):404-11. doi: 10.1093/jjco/hyp192. Epub 2010 Feb 4.
ABI-007 is a novel Cremophor EL-free nanoparticle albumin-bound paclitaxel. This Phase I study was designed to evaluate tolerability and determine recommended dose for Japanese patients when ABI-007 was administered in every-3-week schedule. Pharmacokinetics of paclitaxel was also assessed.
Patients with advanced solid tumors refractory to standard therapy received a 30 min intravenous infusion of ABI-007 every 3 weeks without pre-medications at 200, 260 or 300 mg/m(2), respectively. Tolerability and recommended dose were determined by the standard '3 + 3' rule.
No dose-limiting toxicity was observed, despite the dose escalation. In another cohort, 260 mg/m(2) was re-evaluated and resulted in no dose-limiting toxicity. Grade 3 or 4 neutropenia was reported for the majority of patients (n = 8) but no incidence of febrile neutropenia. Non-hematological toxicities were generally mild except for Grade 3 sensory neuropathy (n = 3). Pharmacokinetic study demonstrated the area under the curve of paclitaxel increased with increasing the dosage, and comparable pharmacokinetic parameters to the western population. Partial response was observed in three non-small cell lung cancer patients. Two of whom had received docetaxel-containing chemotherapy prior to the study.
ABI-007 administered in every-3-week schedule was well tolerated up to 300 mg/m(2), and recommended dose was determined at 260 mg/m(2) in consideration of efficacy, toxicities and similarity of pharmacokinetic profile in western studies. Additional studies of single-agent ABI-007 as well as platinum-based combinations, particularly in patients with non-small cell lung cancer, are warranted.
ABI-007 是一种新型无聚氧乙烯蓖麻油白蛋白结合紫杉醇纳米粒。本研究旨在评估日本患者每 3 周接受 ABI-007 治疗的耐受性和确定推荐剂量。还评估了紫杉醇的药代动力学。
对标准治疗无效的晚期实体瘤患者分别以 200、260 或 300mg/m2 的剂量，30 分钟静脉输注 ABI-007，每 3 周一次，不预先给予药物。耐受性和推荐剂量采用标准的“3+3”规则确定。
尽管进行了剂量递增，但未观察到剂量限制毒性。在另一队列中，重新评估了 260mg/m2 的剂量，结果未观察到剂量限制毒性。大多数患者（n=8）出现 3 级或 4 级中性粒细胞减少，但无发热性中性粒细胞减少。除 3 级感觉神经病（n=3）外，非血液学毒性通常较轻。药代动力学研究表明，随着剂量的增加，紫杉醇的曲线下面积增加，与西方人群的药代动力学参数相当。3 例非小细胞肺癌患者观察到部分缓解。其中 2 例在研究前接受了含多西紫杉醇的化疗。
在每 3 周的治疗方案中，ABI-007 耐受性良好，最高剂量可达 300mg/m2，考虑到疗效、毒性和与西方研究相似的药代动力学特征，确定推荐剂量为 260mg/m2。需要进一步研究 ABI-007 单药治疗以及铂类联合治疗，特别是在非小细胞肺癌患者中。
