A phase II study of NK012, a polymeric micelle formulation of SN-38, in unresectable, metastatic or recurrent colorectal cancer patients.
A phase II study of NK012, a polymeric micelle formulation of SN-38, in unresectable, metastatic or recurrent colorectal cancer patients.
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NK012的II期研究是一种不可切除的，转移或复发性的结直肠癌患者的SN-38的聚合物胶束制剂。
DOI：
10.1007/s00280-018-3693-6
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发表时间：
2018-12
影响因子：
3
通讯作者：
Tsukamoto T
中科院分区：
文献类型：
--
作者：
Hamaguchi T;Tsuji A;Yamaguchi K;Takeda K;Uetake H;Esaki T;Amagai K;Sakai D;Baba H;Kimura M;Matsumura Y;Tsukamoto T
NK 012是SN-38（伊立替康的活性代谢产物）的聚合物胶束制剂。我们评估了NK 012在日本不可切除的转移性结直肠癌患者中的疗效和安全性。我们在58例接受过基于奥沙利铂的化疗方案治疗的患者中进行了一项NK 012单药治疗的多中心开放标签II期试验（A组：53例UGT 1A 1基因型-/-、*6/-或 *28/-患者; B组：5例UGT 1A 1基因型 *6/*28或 *6/*6患者）。主要终点是反应率（RR）。A组和B组的初始剂量分别为28和18 mg/m2，在30 min内静脉给药，随后每3周一次。A组被评估为主要疗效人群，而B组被评估为参考人群。A组的RR为3.8%，中位无进展生存期和总生存期分别为3.30个月和15.03个月。两组中最常见的≥ 3级药物不良反应（ADR）为中性粒细胞减少，≥ 3级腹泻的发生率较低或为零。在A组中，在10例患者（17%）中观察到17起严重ADR;所有ADR均得到改善或恢复。B组无严重不良反应。两组均未报告治疗相关死亡。NK 012单药治疗产生的RR与III期EPIC试验中报告的伊立替康单药治疗的RR相似（4.2%），≥ 3级腹泻的发生率较低。根据发热性中性粒细胞减少症和≥ 3级中性粒细胞减少症的发生率和严重程度，对于既往接受过含奥沙利铂化疗方案治疗的结直肠癌患者，NK 012 28 mg/m2的初始剂量可能过高。
NK012 is a polymeric micelle formulation of SN-38, the active metabolite of irinotecan. We evaluated the efficacy and safety of NK012 in Japanese patients with unresectable metastatic colorectal cancer. We conducted a multicenter open-label phase II trial of NK012 monotherapy in 58 patients who had been treated with an oxaliplatin-based chemotherapy regimen (group A: 53 patients with UGT1A1 genotype –/–, *6/–, or *28/–; group B: 5 patients with UGT1A1 genotype *6/*28 or *6/*6). The primary endpoint was the response rate (RR). Initial doses of 28 and 18 mg/m2 for group A and group B, respectively, were administered intravenously over 30 min, and these doses were subsequently administered every 3 weeks. Group A was evaluated as the primary efficacy population, while group B was evaluated for reference. In group A, the RR was 3.8%, and the median progression-free survival and overall survival were 3.30 months and 15.03 months, respectively. In both groups, the most common grade ≥ 3 adverse drug reaction (ADR) was neutropenia and the incidence of grade ≥ 3 diarrhea was low or zero. In group A, 17 serious ADRs were observed in 10 patients (17%); all improved or recovered. In group B, no serious ADRs were observed. No treatment-related deaths were reported in either group. NK012 monotherapy yielded an RR similar to the RR of irinotecan monotherapy that was reported in the phase III EPIC trial (4.2%), and the incidence of grade ≥ 3 diarrhea was low. Based on the incidence and severity of febrile neutropenia and grade ≥ 3 neutropenia, the initial dose of NK012 28 mg/m2 may be too high for colorectal cancer patients who have previously been treated with an oxaliplatin-based chemotherapy regimen.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
1.9
作者：
FLEMING, TR
通讯作者：
FLEMING, TR
影响因子：
1.8
作者：
ATSUMI, R;SUZUKI, W;HAKUSUI, H
通讯作者：
HAKUSUI, H
影响因子：
5.7
作者：
Saito, Yohei;Yasunaga, Masahiro;Matsumura, Yasuhiro
通讯作者：
Matsumura, Yasuhiro
影响因子：
8.8
作者：
Guichard, S;Terret, C;Hennebelle, I;Lochon, I;Chevreau, P;Frétigny, E;Selves, J;Chatelut, E;Bugat, R;Canal, P
通讯作者：
Canal, P