Phase II study of daily oral perifosine in patients with advanced soft tissue sarcoma
Phase II study of daily oral perifosine in patients with advanced soft tissue sarcoma
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DOI：
10.1002/cncr.22308
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发表时间：
2006-11-15
期刊：
影响因子：
6.2
通讯作者：
Okuno, Scott H.
中科院分区：
文献类型：
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作者：
Bailey, Howard H.;Mahoney, Michelle R.;Okuno, Scott H.
背景资料。对晚期软组织肉瘤(STSS)患者进行了一项多中心II期研究，以评估初始剂量(每6小时150毫克×4剂)和连续每日口服(100毫克/天)周围素的临床活性。方法：可测量的转移性STS患者接受周围素作为第一线、第二线或第三线治疗，并每8周接受一次疾病评估，直到疾病进展、过度毒性或患者复发。结果：23名患者接受了66个周期(1周期=4周)的周福辛治疗。1例部分缓解，持续时间9个月。总的3个月和6个月无进展生存率分别为22%和9%。NCI CTC(v2.0)1-2级胃肠道毒性或疲劳是最常见的毒性(占受试者的50%)。稳态血药浓度(CS)与既往经验相似(平均为6微克/毫升)。在过去的2个月中，css水平为6mU/m L的患者比css水平为6mU/m L的患者更有可能继续接受研究。结论：尽管没有达到>；40%的6个月无进展生存率的主要目标，STS患者仍然对这种药物持乐观态度。在重度预处理的STS患者中，持续的反应继续被观察到周效磷脂治疗。继续对STS患者的周磷脂进行评估似乎是有必要的，特别要注意特定的组织学或肿瘤特征，以确定更敏感的人群，并达到周磷脂水平>；6微克/毫升。
BACKGROUND. A multicenter Phase II study was performed to evaluate the clinical activity of an initial loading (150 mg every 6 hours x 4 doses) dose followed by continuous daily oral dosing (100 mg/day) of perifosine in patients with advanced soft tissue sarcomas (STSs).METHODS. Patients with measurable metastatic STS received perifosine as first-, second-, or third-line treatment and underwent disease assessment every 8 weeks until disease progression, excessive toxicity, or patient refusal.RESULTS. Twenty-three patients received 66 cycles (1 cycle = 4 weeks) of perifosine. One partial response of 9 months duration was observed. The overall 3 and 6 month progression-free survival was 22% and 9%. NCI CTC (v2.0) Grade 1 to 2 gastrointestinal toxicity or fatigue were the most common (> 50% of subjects) toxicities observed. The steady-state plasma perifosine levels (Css) were similar to prior experience (mean 6 mu g/mL). Patients with Css levels > 6 mu g/mL appeared more likely to remain on study past 2 months than those with levels < 6 mu g/mL.CONCLUSIONS. Despite not achieving the primary objective of > 40% 6-month progression-free survival rate, optimism remains for this agent in STS patients. Prolonged responses in heavily pretreated STS patients continue to be observed with perifosine treatment. Continued assessment of perifosine in STS appears warranted, with special attention to specific histologies or tumor characteristics that might identify a more sensitive population and achieving perifosine Css levels > 6 mu g/mL.