The Royal Marsden, Downs Road, Sutton, SM2 5PT, UK.
Invest New Drugs. 2013 Oct;31(5):1339-44. doi: 10.1007/s10637-013-9990-3. Epub 2013 Jun 26.
Phase I trials of the microtubule stabilising agent patupilone showed encouraging tumour control and response rates in patients with metastatic colorectal cancer.
Patients with metastatic or locally recurrent colorectal cancer who had progressed following treatment with oxaliplatin, irinotecan and fluoropyrimidines were treated with patupilone (8 mg/m(2) IV every 3 weeks) in combination with dexamethasone or prednisolone.
The trial was closed early after 29 patients had been enrolled due to concerns about toxicity. 20 patients (71.4 %) experienced at least one grade 3-5 toxicity, most commonly diarrhoea (14 patients), dehydration (7 patients) and lethargy (6 patients). The 12 week progression-free survival rate was 16.7 % (95 % CI 6.1 %-36.5 %) in the 24 patients with a 12 week scan available or who had died prior to the 12 week scan. No complete or partial responses were seen by 12 weeks. The median progression-free survival was 2.6 months (95 % CI 2.3-2.9) and median overall survival was 6.1 months (95 % CI 3.7-8.4).
Patupilone given at a dose of 8 mg/m(2) IV over 20 min every 3 weeks was associated with high levels of toxicity and no significant evidence of efficacy in patients with pre-treated colorectal cancer.
微管稳定剂帕他泊隆的 I 期试验显示转移性结直肠癌患者具有令人鼓舞的肿瘤控制和缓解率。
转移性或局部复发性结直肠癌患者在接受奥沙利铂、伊立替康和氟嘧啶治疗后进展，给予帕他泊隆（8 mg/m2 IV 每 3 周一次）联合地塞米松或泼尼松龙治疗。
由于对毒性的担忧，该试验在 29 名患者入组后提前关闭。20 名患者（71.4%）出现至少 1 次 3-5 级毒性，最常见的是腹泻（14 例）、脱水（7 例）和嗜睡（6 例）。24 名有 12 周扫描结果或在 12 周扫描前死亡的患者中，12 周无进展生存率为 16.7%（95%CI 6.1%-36.5%）。12 周时未观察到完全或部分缓解。无进展生存期的中位数为 2.6 个月（95%CI 2.3-2.9），总生存期的中位数为 6.1 个月（95%CI 3.7-8.4）。
在预处理的结直肠癌患者中，8 mg/m2 IV 帕他泊隆 20 分钟输注，每 3 周 1 次，与高毒性相关，且无明显疗效证据。
