Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study.
Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study.
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DOI：
10.1186/1471-2407-13-263
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发表时间：
2013-05-29
期刊：
影响因子：
3.8
通讯作者：
Samantas E
中科院分区：
文献类型：
--
作者：
Briasoulis E;Aravantinos G;Kouvatseas G;Pappas P;Biziota E;Sainis I;Makatsoris T;Varthalitis I;Xanthakis I;Vassias A;Klouvas G;Boukovinas I;Fountzilas G;Syrigos KN;Kalofonos H;Samantas E
节律化疗被认为是一种抗血管生成治疗，包括在短时间内定期进行低剂量的慢性化疗。我们研究了转移性癌症患者单药口服长春瑞滨的最佳剂量。复发性转移性乳腺癌（BC）、前列腺癌（PC）或非小细胞肺癌（NSCLC）且器官功能正常的患者随机分配服用30,40或50mg长春瑞滨，每周口服3次。治疗持续至疾病进展、不可接受的毒性、撤回同意或最多24个月。主要终点是治疗失败时间（TTF），次要终点是无进展生存期（PFS）、毒性、血管生成相关生物标志物的血药浓度变化和药代动力学。73名患者入组。四个月TTF率在三个组之间没有差异：30 mg、40 mg和50 mg组分别为25.9%（11.1%-46.2% 95%可信区间）、33.3%（15.6%-55.3%）和18.2% (5.2%-40.3%)（p值= 0.56）。2例NSCLC患者（分别用30mg和50mg治疗）、1例BC患者（40mg）和1例PC患者（50mg）出现客观反应，持续时间为4至100周，50mg时达到最大反应持续时间。不良事件轻微，可以忽略不计，三个组之间没有差异。从治疗第二周开始，维诺瑞滨血液水平达到稳定状态，30mg、40mg和50mg的平均值分别为1.8 ng/ml （SD 1.10）、2.2 ng/ml （SD 1.87）和2.6 ng/ml （SD 0.69）。治疗前血液中FGF2和IL8的低浓度预示着对治疗的有利反应（p值分别为0.02和0.006），而高水平的TEK基因转录物预示着治疗耐药性。考虑到抗肿瘤活性和反应持续时间，所研究的最高剂量的毒性可以忽略不计，以及药物随时间积累的不足，我们建议每周三次，每次50mg是节拍节拍口服长春瑞滨的最佳剂量。进一步研究这一剂量的节拍口服长春瑞滨（MOVIN）与常规化疗方案和靶向治疗的联合治疗是必要的。Clinicaltrials.gov NCT00278070
Metronomic chemotherapy is considered an anti-angiogenic therapy that involves chronic administration of low-dose chemotherapy at regular short intervals. We investigated the optimal metronomic dose of oral vinorelbine when given as monotherapy in patients with metastatic cancer. Patients with recurrent metastatic breast (BC), prostate (PC) or non-small cell lung cancer (NSCLC) and adequate organ functions were randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three times a week. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or maximum 24 months. Primary endpoint was time-to-treatment failure (TTF) and secondary were progression-free survival (PFS), toxicity, changes in blood concentrations of angiogenesis-associated biomarkers and pharmacokinetics. Seventy-three patients were enrolled. Four-month TTF rate did not differ between the three arms: 25.9% (11.1%-46.2% 95% Confidence Interval), 33.3% (15.6%-55.3%) and 18.2% (5.2%-40.3%) for the 30 mg, 40 mg and 50 mg arms (p-value = 0.56). Objective response was seen in 2 patients with NSCLC (treated at 30 and 50 mg respectively), one with BC (at 40 m g) and one with PC (at 50 mg) and lasted from 4 to 100 weeks, with maximum response duration achieved at 50 mg. Adverse events were mild and negligible and did not differ between the three arms. Blood levels of vinorelbine reached steady state from the second week of treatment and mean values for the 30, 40 and 50 mg were respectively 1.8 ng/ml (SD 1.10), 2.2 ng/ml (SD 1.87) and 2.6 ng/ml (SD 0.69). Low pre-treatment blood concentrations of FGF2 and IL8 predicted favorable response to therapy (p values 0.02 and 0.006, respectively), while high levels of TEK gene transcript predicted treatment resistance. Considering the antitumor activity and response duration, the negligible toxicity of the highest dose investigated and the lack of drug accumulation over time, we suggest that 50 mg given three times a week is the optimal dose for metronomic oral vinorelbine. Further investigation of metronomic oral vinorelbine (MOVIN) at this dose is warranted in combination with conventional chemotherapy regimens and targeted therapies. Clinicaltrials.gov NCT00278070
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影响因子：
20.3
作者：
Hamaguchi, I;Huang, XL;Suda, T
通讯作者：
Suda, T
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Huang D;Ding Y;Zhou M;Rini BI;Petillo D;Qian CN;Kahnoski R;Futreal PA;Furge KA;Teh BT
通讯作者：
Teh BT
影响因子：
12.4
作者：
Chen, Chi-An;Ho, Chih-Ming;Cheng, Wen-Fang
通讯作者：
Cheng, Wen-Fang
影响因子：
2
作者：
Hahnfeldt, P;Folkman, J;Hlatky, L
通讯作者：
Hlatky, L