TAS-106 联合卡铂治疗实体瘤患者的 I 期剂量递增研究。
Phase I dose-escalating study of TAS-106 in combination with carboplatin in patients with solid tumors.
机构信息
Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX, 77030, USA,
出版信息
Invest New Drugs. 2014 Feb;32(1):154-9. doi: 10.1007/s10637-013-9964-5. Epub 2013 Apr 23.
BACKGROUND
TAS-106 was designed to inhibit RNA synthesis by blocking RNA polymerases I, II, and III.
METHODS
This was a single-center, open-label, phase I study to identify the maximum tolerated dose (MTD), pharmacokinetics, and biologic effects of the combination of TAS-106 and carboplatin, following a standard 3 + 3 design. This phase I trial was comprised of a regimen of a 60-min IV infusion of carboplatin on day 1 of each 21-day cycle followed by a 24-h infusion of TAS-106, also on day 1 of each cycle.
RESULTS
39 patients were treated (21 male, 18 female, median age 62 years, range 21-80 years). Median number of prior therapies was 4. Maximum Tolerated Dose (MTD) was 3 mg/m(2) TAS-106 with AU 4 carboplatin. Dose-limiting toxicities were neutropenia and thrombocytopenia, with and without growth factor support. While no patients achieved a complete or partial response, four patients had stable disease lasting ≥4 months, including one patient each with ovarian, non-small cell lung, basal cell and colorectal cancer.
CONCLUSIONS
In summary, the combination of TAS-106 and carboplatin was well-tolerated, and further studies in non-small cell lung and ovarian cancer are warranted to assess the efficacy of this drug combination.
背景
TAS-106 的设计目的是通过阻断 RNA 聚合酶 I、II 和 III 来抑制 RNA 合成。
方法
这是一项单中心、开放性、I 期研究，旨在确定 TAS-106 联合卡铂的最大耐受剂量（MTD）、药代动力学和生物学效应，采用标准的 3+3 设计。该 I 期试验包括在每个 21 天周期的第 1 天给予 60 分钟 IV 输注卡铂，随后在每个周期的第 1 天给予 24 小时输注 TAS-106。
结果
39 名患者接受了治疗（21 名男性，18 名女性，中位年龄 62 岁，范围 21-80 岁）。中位数既往治疗次数为 4 次。TAS-106 的最大耐受剂量（MTD）为 3mg/m2，卡铂 AU4。剂量限制性毒性是中性粒细胞减少和血小板减少，有或没有生长因子支持。虽然没有患者达到完全或部分缓解，但有 4 名患者的疾病稳定持续≥4 个月，包括卵巢癌、非小细胞肺癌、基底细胞癌和结直肠癌各 1 例。
结论
总之，TAS-106 联合卡铂耐受性良好，需要进一步在非小细胞肺癌和卵巢癌中进行研究，以评估这种药物联合的疗效。
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