Department of Clinical and Biological Science, University of Turin, Azienda Ospedaliero Universitaria San Luigi, Regione Gonzole 10, 10043 Orbassano, Italy.
Eur J Endocrinol. 2012 Mar;166(3):451-8. doi: 10.1530/EJE-11-0918. Epub 2011 Dec 21.
There is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.
We assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro.
Multicenter, prospective phase II trial. Setting Referral centers for ACC.
Twenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m(2) every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.
Tumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose-response and time-response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel.
Despite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.
在肾上腺皮质癌（ACC）的治疗中，使用抗血管生成疗法具有很强的原理。节拍化疗和抗血管生成药物的联合治疗可以协同靶向内皮细胞。
我们评估了索拉非尼联合节拍紫杉醇作为晚期 ACC 患者二线/三线治疗的疗效。我们还测试了索拉非尼和紫杉醇对 NCI-H295R 的体外活性。
多中心、前瞻性 II 期试验。设置 ACC 转诊中心。
计划招募 25 例转移性 ACC 患者，这些患者在米托坦加用一种或两种化疗方案后进展。患者接受静脉注射紫杉醇（60 mg/m²，每周一次）和口服索拉非尼（400 mg，每天两次）联合治疗，直至进展。主要目的是测量 4 个月后的无进展生存率，次要目的是评估客观缓解率和毒性。
在首次评估时，9 例可评估患者观察到肿瘤进展。这些结果导致试验提前终止。治疗耐受性良好。最相关的毒性是疲劳，4 例患者为 2 级或 3 级，3 例患者为 3 级低磷血症。在体外研究中，索拉非尼以剂量-反应和时间-反应关系损害了 H295R 细胞的活力。紫杉醇联合索拉非尼并未增加体外索拉非尼的活性。
尽管有体外活性，但索拉非尼联合每周紫杉醇作为晚期 ACC 患者的挽救性治疗是无效的，不应推荐。
