Lessons Learned. endpoint was enough time to treatment failure (TTTF) (i.e. radiological and/or symptomatic progression). The secondary endpoints included the tumor response rate (RECIST 1.0) security (National Malignancy Institute Common Terminology Criteria for Adverse Events version 3.0) quality of life (Functional Assessment of Malignancy Therapy-Prostate [FACT-P]) pain (Present Pain Intensity [PPI] level) prostate-specific antigen (PSA) parameters including time to PSA progression (TTPP) according to Prostate Malignancy Clinical Trials Working Group criteria and serial enumeration of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs). Results. Patients received a median of 7 cycles of temsirolimus (range 1 resulting in a median TTTF of 24.3 weeks (95% confidence interval [CI] 16.1 1 partial tumor response (4.8%) 1 PSA response (4.8%) and a median TTPP of 12.2 weeks (95% CI 7.8 Grade 3-4 adverse events were FACT-P and infrequent and PPI scores remained steady during treatment. CECs didn’t predict clinical advantage and CEPs weren’t detectable consistently. Bottom line. Temsirolimus maintenance therapy after effective docetaxel induction is certainly feasible will not adversely have an effect on standard of living and in this exploratory single-arm stage II research led to a median TTTF of 24.3 weeks. Abstract 经验 替西罗莫司用于多西他赛诱导化疗后的维持治疗 ? 可安全地用于去势难治性前列腺癌患者 尽管生物化学或肿瘤缓解罕见; ? 不会损害生活质量 并且 ? 可使放射学和(或)症状性进展推迟约6个月。 摘要 对于多西他赛治疗有效且尚未发生疾病进展的去势难治性前列腺癌(CRPC)男性患者 目前尚无标准治疗。因此我们设计了一项单臂II期临床试验 旨在探索mTOR抑制剂替西罗莫司能否维持多西他赛的疗效而不损害患者生活质量。 21 mg/m2每3周一次 6 ～ 10周期)治疗成功后接受了替西罗莫司维持治疗(25 mg每周一次 每周期4周)。主要终点为至治疗失败时间(TTTF)[即放射学和(或)症状性进展]。次要终点包括肿瘤缓解率(RECIST 1.0)、安全性(美国国家癌症研究所常见不良反应事件评价标准3.0版本)、生活质量[前列腺癌治疗功能评价(FACT-P)]、疼痛[现时疼痛强度(PPI)量表] 以及前列腺特异性抗原(PSA)参数 包括依据前列腺癌临床试验工作组标准判定的至PSA进展时间(TTPP)以及循环内皮细胞(CEC)和内皮祖细胞(CEP)的连续计数。 替西罗莫司中位治疗周期为7周期(范围1 ～ 28) 中位TTTF为24.3周[95%置信区间(CI):16.1 ～ 33.0] 1 中位TTPP为12.2周(95%CI:7.8 ～ 23.9)。治疗期间3/4级不良事件少见 且FACT-P和PPI评分保持稳定。CEC不能预测临床获益 CEP不能持续检出。 多西他赛诱导治疗成功后使用替西罗莫司维持治疗可行且不损害生活质量。本项探索性II期单臂研究中达到了24.3周的中位TTTF。2015;20:1351-1352 Writer Summary SB 216763 Debate In the lack of development or prohibitive toxicity docetaxel chemotherapy is normally administered for 10 cycles for the treating Rabbit Polyclonal to USP6NL. SB 216763 CRCP. The perfect duration of docetaxel therapy is not determined Nevertheless. Instead of treating to development or even to a finite variety of cycles two different strategies have already been explored in primary research: (a) intermittent docetaxel chemotherapy (supplemental on the web Desk 1 [obtainable on the web]); and (b) maintenance therapy using several agents (supplemental on the web Desk 2 [obtainable on the web]). We present the results from the first research of temsirolimus maintenance therapy in 21 CRPC sufferers after effective SB 216763 docetaxel induction. The rapalog mTOR inhibitor (mTORi) temsirolimus was selected due to the higher rate of PI3K-AKT-mTOR pathway abnormalities in CRPC preclinical temsirolimus activity in a variety of prostate cancer versions and the good basic safety profile of rapalog mTORis. Temsirolimus maintenance therapy led to a median TTTF of 24.3 weeks (95% CI 16.1 (Fig. 1A; Desk 2 [obtainable online]). Biochemical development preceded symptomatic (61.9%) and/or radiological (23.8%) development in most sufferers accounting for the TTPP of 12.14 times (95% CI 7.8 (Fig. 1A 1 Desk 2 [obtainable online]). Apart from an individual PSA and a incomplete tumor response we noted any PSA drop in 10 of 20 evaluable sufferers and steady disease was seen in 61.9% of patients (Fig. 1C; Desk 2 [obtainable online]). Quality 3 treatment-related unwanted effects such as for example hyperglycemia had been infrequent (9.5%) and one quality 4 thromboembolic event occurred. One affected individual withdrew consent due to quality 2 peripheral edema regarded “perhaps” treatment related. Temsirolimus didn’t diminish standard of living as evaluated using the FACT-P questionnaire (Fig. 2A) nor do we observe significant adjustments in discomfort (Fig. 2B) or functionality status (data not really proven) during treatment. Body 1. Treatment final results. (A): The median TTTF (i.e. radiological and/or symptomatic development) was 24.3 weeks (95% CI 16.1 The TTPP was 12.14 times (95% CI 7.8 (B): Depiction of TTPP (white bars) TTTF (gray bars) and OS … Our findings confirm the typically cytostatic effects of rapalog SB 216763 mTORis observed in different stages of CRPC (supplemental online Table 3 [available online]) possibly due to only partial.