Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan.
Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan.
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DOI：
10.1186/s12885-015-1675-1
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发表时间：
2015-10-09
期刊：
影响因子：
3.8
通讯作者：
Japan RCC Trialist Collaborative Group (JRTCG) investigators
中科院分区：
文献类型：
--
作者：
Eto M;Kawano Y;Hirao Y;Mita K;Arai Y;Tsukamoto T;Hashine K;Matsubara A;Fujioka T;Kimura G;Shinohara N;Tatsugami K;Hinotsu S;Naito S;Japan RCC Trialist Collaborative Group (JRTCG) investigators
为了提高对转移性肾细胞癌（mRCC）的抗肿瘤效果，提倡在序贯或联合治疗中使用基于分子靶向的药物。在联合治疗中，干扰素（IFN）-α在我们的鼠模型中放大了索拉非尼的作用（J Urol 184：2549，2010），并且日本的马槟榔碱治疗的mRCC患者具有良好的预后（Eur Urol 57：317，2010）。因此，我们在日本进行了索拉非尼联合IFN-α治疗未经治疗的mRCC患者的II期临床试验。在这项多中心、前瞻性研究中，组织学证实的转移性透明细胞RCC的临时登记患者接受天然IFN-α（每周3次，每次300万U）治疗2周。仅IFN-α耐受患者登记参加本试验，并额外接受口服索拉非尼（400 mg，bid）治疗。研究的主要终点是使用RECIST v1.0评估的索拉非尼+IFN-α治疗的应答率（CR + PR）。次要终点为疾病控制率（CR + PR + SD）、无进展生存期（PFS）、总生存期（OS）和联合治疗的安全性。使用Kaplan-Meier方法绘制PFS和OS曲线。2009年7月至2012年7月，共有53名未经治疗的患者临时登记，51名患者最终登记。索拉非尼联合IFN-α治疗的有效率为26.2%（11/42）（CR 1，PR 10）。中位PFS为10.1个月（95% CI，6.4 - 18.5个月），尚未达到中位OS。联合治疗既没有增加不良反应（AE）的发生率，也没有增加非预期AE的发生率。局限性是因违反合格性标准而排除的患者数量相对较高（9例患者）。我们的数据表明，索拉非尼联合IFN-α治疗对未经治疗的mRCC患者是安全有效的。UMIN 000002466，2009年9月9日本文的在线版本（doi：10.1186/s12885-015-1675-1）包含补充材料，授权用户可以使用。
To improve antitumor effects against metastatic renal cell carcinoma (mRCC), use of molecular target-based drugs in sequential or combination therapy has been advocated. In combination therapy, interferon (IFN)-α amplified the effect of sorafenib in our murine model (J Urol 184:2549, 2010), and cytokine-treated mRCC patients in Japan had good prognoses (Eur Urol 57:317, 2010). We thus conducted a phase II clinical trial of sorafenib plus IFN-α for untreated mRCC patients in Japan. In this multicenter, prospective study, provisionally registered patients with histologically confirmed metastatic clear cell RCC received natural IFN-α (3 dosages of 3 million U per week) for 2 weeks. Only IFN-α-tolerant patients were registered to this trial, and treated additionally with oral sorafenib (400 mg, bid). The primary end point of the study was rate of response (CR + PR) to sorafenib plus IFN-α treatment assessed using RECIST v1.0. The secondary end points were disease control rate (CR + PR + SD), progression free survival (PFS), overall survival (OS), and safety of the combined treatment. PFS and OS curves were plotted using the Kaplan-Meier method. From July 2009 to July 2012, a total of 53 untreated patients were provisionally registered, and 51 patients were finally registered. Rate of Response to the combined therapy of sorafenib plus IFN-α was 26.2 % (11/42) (CR 1, PR 10). The median PFS was 10.1 months (95 % CI, 6.4 to 18.5 months), and the median OS has not been reached yet. The combined therapy increased neither the incidence of adverse effects (AE) nor the incidence of unexpected AE. A limitation was that a relatively high number of patients (9 patients) were excluded for eligibility criteria violations. Our data have demonstrated that sorafenib plus IFN-α treatment is safe and effective for untreated mRCC patients. UMIN000002466, 9th September, 2009 The online version of this article (doi:10.1186/s12885-015-1675-1) contains supplementary material, which is available to authorized users.