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PI3K抑制剂XC302连续给药治疗晚期实体肿瘤的I期临床耐受性试验 被引量:1

A Phase I Tolerability Study of XC302, a PI3K Inhibitor, Administered Daily in Chinese Patients with Advanced Solid Tumors
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摘要 【目的】确定PI3K抑制剂XC302连续口服给药的剂量限制性毒性(DLT)和最大耐受剂量(MTD),评估其耐受性并初步观察XC302治疗晚期实体肿瘤患者的疗效。【方法】常规治疗失败的晚期实体肿瘤患者分别进入4个组别接受XC302每天1次或每天2次口服治疗,起始剂量为50 mg/d,按"3+3"模式进行剂量递增或根据前一阶段试验结果调整。根据NCI-CTCAE 3.0版毒性评定标准评估不良反应。按RECIST 1.0版标准进疗效评估。【结果】共入组30例晚期肿瘤患者。XC302连续给药常见的不良反应包括白细胞减少(23.3%)、血红蛋白下降(30%)、恶心(20%)、谷丙转氨酶(ALT)升高(63.3%)及谷草转氨酶升高(AST)(50%)、碱性磷酸酶升高(ALP)(23.3%)和谷氨酰转肽酶升高(GGT)(26.7%)。DLT为可逆的3度ALT和AST升高。MTD为100 mg每天一次(空腹)及75 mg qd(餐后)。23例患者进行了疗效评价,12例(52.5%)达到稳定(SD)。有1例软组织肉瘤患者无进展生存期(PFS)长达64周。【结论】PI3K抑制剂XC302连续口服给药总体耐受性良好且治疗晚期实体肿瘤有较高的疾病控制率,值得进一步研究。 [Objective] To determine the dose limited toxicities and maximum tolerated dose of continuous daily XC302 in Chinese patients with advanced solid tumors,as well as it's tolerability and preliminary antitumor activity.[Methods] Patients with histologically confirmed advanced/refractory solid tumors were assigned into 4 cohorts to received oral XC302 once or twice daily.Dosing of XC302 escalated from 50 mg/d and guided by a "3+3"model or modified according to previous results.Adverse events were recorded according to NCI CTCAE version 3.0.Assessment of response was performed radiologically according to RECIST version 1.0.[Results] Totally 30 patients were enrolled.Frequent treatment-related adverse events included leukopenia (23.3%),Ganemia (30%),nausea (20%),increased ALT (63.3%)/AST (50%)/ALP (23.3%)/GGT (26.7%) levels.Reversible abnormal hepatic function (increased ALT/AST levels) was documented as it's DLT.MTD for continuous administration of XC302 was 100 mg qd (fasting) and 75mg qd (postprandial).Best overall response was stable disease for 12 of 23 patients who underwent response evaluation,including one experienced long PFS of 64 weeks.[Conclusion] Continuous daily XC302 treatment demonstrates a manageable safety profile and promising disease control rate in Chinese patients with advanced solid tumors,which deserves further investigation.
出处 《中山大学学报(医学科学版)》 CAS CSCD 北大核心 2015年第3期414-420,共7页 Journal of Sun Yat-Sen University:Medical Sciences
基金 “十一五”国家科技重大专项(2008ZXO09312-002)
关键词 PI3K抑制剂 临床试验 耐受性 肿瘤 PI3K inhibitor clinical trial tolerability tumor
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