Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
J Clin Oncol. 2010 Apr 1;28(10):1780-7. doi: 10.1200/JCO.2009.25.5208. Epub 2010 Mar 1.
Thymosin alpha 1 (Talpha1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Talpha1 with dacarbazine (DTIC) and interferon alfa (IFN-alpha) in patients with metastatic melanoma.
Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-alpha+Talpha1 (1.6 mg); DTIC+IFN-alpha+Talpha1 (3.2 mg); DTIC+IFN-alpha+Talpha1 (6.4 mg); DTIC+Talpha1 (3.2 mg); DTIC+IFN-alpha (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months.
Ten and 12 tumor responses were observed in the DTIC+IFN-alpha+Talpha1 (3.2 mg) and DTIC+Talpha1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P(0) < or = .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Talpha1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Talpha1 versus 6.6 months in the control group (hazard ratio = 0.80; 9% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Talpha1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Talpha1 to DTIC and IFN-alpha did not lead to any additional toxicity.
These results suggest Talpha1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.
胸腺肽 α1（Talpha1）是一种免疫调节多肽，可增强效应 T 细胞的反应。在这项大型随机研究中，我们评估了泰莫西芬联合达卡巴嗪（DTIC）和干扰素 α（IFN-α）治疗转移性黑色素瘤患者的疗效和安全性。
488 名患者被随机分配到五组治疗组：DTIC+IFN-α+Talpha1（1.6 mg）；DTIC+IFN-α+Talpha1（3.2 mg）；DTIC+IFN-α+Talpha1（6.4 mg）；DTIC+Talpha1（3.2 mg）；DTIC+IFN-α（对照组）。主要终点是研究结束时（12 个月）的最佳总体反应。次要终点包括反应持续时间、总生存期（OS）和无进展生存期（PFS）。患者观察时间最长达 24 个月。
DTIC+IFN-α+Talpha1（3.2 mg）和 DTIC+Talpha1（3.2 mg）组分别观察到 10 例和 12 例肿瘤反应，而对照组为 4 例，足以拒绝 P（0）<或=0.05（标准治疗预期反应率）的零假设在这两个组中。接受 Talpha1 治疗的患者的反应持续时间从 1.9 个月到 23.2 个月不等，而对照组为 4.4 个月至 8.4 个月。接受 Talpha1 治疗的患者中位 OS 为 9.4 个月，对照组为 6.6 个月（风险比=0.80；9%CI，0.63 至 1.02；P=0.08）。与对照组相比，接受 Talpha1 治疗的患者 PFS 增加（风险比=0.80；95%CI，0.63 至 1.01；P=0.06）。Talpha1 联合 DTIC 和 IFN-α 不会导致任何额外的毒性。
这些结果表明 Talpha1 对转移性黑色素瘤患者具有活性，并为进一步评估该药物的临床应用提供了依据。
