第二阶段研究kx2 - 391,口服Src激酶抑制剂和微管蛋白聚合,在男性bone-metastatic castration-resistant前列腺癌。

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Antonarakis,希思EI、波萨达斯EM Yu EY、哈里森先生,布鲁斯·司法院赵SY,野生的通用电气,羁绊GJ, Hangauer DG,关颖珊MF,马Dyster LM,性格外向

第二阶段研究kx2 - 391,口服Src激酶抑制剂和微管蛋白聚合,在男性bone-metastatic castration-resistant前列腺癌。

癌症Chemother杂志。2013年4月,71 (4):883 - 92。doi: 10.1007 / s00280 - 013 - 2079 - z。Epub 2013年1月13日。

PubMed ID
23314737 (在PubMed
]
文摘

目的:kx2 - 391是口服non-ATP-competitive Src激酶抑制剂和微管蛋白聚合。在第一阶段试验中,前列腺特异性抗原(PSA)下降晚期前列腺癌患者。单组第二阶段我们进行了一项研究评估kx2 - 391男性chemotherapy-naive bone-metastatic castration-resistant前列腺癌(CRPC)。方法:我们31日患者口服kx2 - 391(40毫克每天),直到疾病进展或不可接受的毒性。主要终点是24周无进展生存(PFS);50%的成功率是预定义的临床意义。次要终点包括PSA无进展生存率(ppf)和PSA响应率。探索性成果包括药代动力学研究中,循环肿瘤细胞(CTC)枚举,和分析的骨吸收标记(尿键(uNTx);C-telopeptide (CTx)]和形成[骨碱性磷酸酶(BAP);骨钙素)。 RESULTS: The trial closed early after accrual of 31 patients, due to a pre-specified futility rule. PFS at 24 weeks was 8 %, and median PFS was 18.6 weeks. The PSA response rate (>/= 30 % decline) was 10 %, and median PPFS was 5.0 weeks. Additionally, 18 % of men with unfavorable (>/= 5) CTCs at baseline converted to favorable (<5) CTCs with treatment. The proportion of men with declines in bone turnover markers was 32 % for uNTx, 21 % for CTx, 10 % for BAP, and 25 % for osteocalcin. In pharmacokinetic studies, median C max was 61 (range 16-129) ng/mL, and median AUC was 156 (35-348) ng h/mL. Common toxicities included hepatic derangements, myelosuppression, fatigue, nausea, and constipation. CONCLUSION: KX2-391 dosed at 40 mg twice-daily lacks antitumor activity in men with CRPC, but has modest effects on bone turnover markers. Because a C max of >/=142 ng/mL is required for tubulin polymerization inhibition (defined from preclinical studies), higher once-daily dosing will be used in future trials.

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药物
药物靶点
药物 目标 类 生物 药理作用 行动
Tirbanibulin 原癌基因酪氨酸受体激酶Src 蛋白质 人类
是的
抑制剂
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