Yale University School of Medicine, New Haven, CT 06520-8032, USA.
Cancer Invest. 2010 Feb;28(2):186-94. doi: 10.3109/07357900903179591.
To determine in patients, with locally advanced or metastatic pancreatic cancer (APC), efficacy and safety of treatment with intravenous paclitaxel loaded polymeric micelle (GPM).
This was a multicenter, open-label Phase II study. Patients with APC, ECOG performance status < or = 2, no prior chemotherapy and adequate organ function were treated with 3-hour GPM infusions every 3 weeks. Initial patients were treated with 435 mg/m(2) (n = 11). The dose was reduced for subsequent patients to 350 or 300 mg/m(2) (n = 45). Primary endpoint was time to tumor progression (TTP).
56 patients were enrolled. Median TTP for patients treated with 300 or 350 mg/m(2) doses was 3.2 months (95% CI, 2.6-4.2). Median progression free survival (PFS) was 2.8 months (95% CI, 1.4-4.0). Median overall survival (OS) was 6.5 months (95% CI, 5.1-7.9). Among patients treated with above doses of GPM, there was 1 complete remission (CR) and 2 partial remissions (PR) with an overall response rate (ORR) of 6.7%. Disease control rate (CR + PR + stable disease) was 60.0%. Most common grade 3 toxicities were: neutropenia (40.0%), fatigue (17.8%), infection, dehydration, neuropathy (each 13.3%), and abdominal pain (11.1%).
Treatment of APC with GPM at a dose of 300 mg/m(2) q 3 weeks was well tolerated and common toxicities were qualitatively similar to Cremophor-based paclitaxel. GPM monotherapy resulted in OS and other efficacy parameters preferable to that seen historically with gemcitabine. Future studies of GPM in combination with other agents for treatment of APC are warranted.
在局部晚期或转移性胰腺腺癌（APC）患者中，确定静脉注射紫杉醇载聚合物胶束（GPM）的疗效和安全性。
这是一项多中心、开放性的 II 期研究。APC 患者，ECOG 表现状态 <或= 2，无先前化疗且器官功能充足，接受每 3 周 3 小时的 GPM 输注。最初的患者接受 435mg/m(2)剂量（n=11）。随后的患者剂量减少至 350 或 300mg/m(2)（n=45）。主要终点是肿瘤进展时间（TTP）。
共纳入 56 例患者。接受 300 或 350mg/m(2)剂量治疗的患者的中位 TTP 为 3.2 个月（95%CI，2.6-4.2）。中位无进展生存期（PFS）为 2.8 个月（95%CI，1.4-4.0）。中位总生存期（OS）为 6.5 个月（95%CI，5.1-7.9）。在接受 GPM 上述剂量治疗的患者中，有 1 例完全缓解（CR）和 2 例部分缓解（PR），总缓解率（ORR）为 6.7%。疾病控制率（CR+PR+稳定疾病）为 60.0%。最常见的 3 级毒性为：中性粒细胞减少（40.0%）、疲劳（17.8%）、感染、脱水、周围神经病变（各 13.3%）和腹痛（11.1%）。
GPM 剂量为 300mg/m(2)每 3 周一次治疗 APC 耐受性良好，常见毒性与基于 Cremophor 的紫杉醇相似。GPM 单药治疗的总生存期和其他疗效参数优于历史上使用吉西他滨的情况。GPM 联合其他药物治疗 APC 的未来研究是必要的。
