1 Department of Surgery, Duke University School of Medicine , Durham, North Carolina.
Thyroid. 2014 Feb;24(2):232-40. doi: 10.1089/thy.2013.0078. Epub 2013 Sep 10.
Anaplastic thyroid cancer (ATC), a rare highly vascularized tumor, has a dismal outcome. We conducted an open-label study of doublet carboplatin/paclitaxel chemotherapy with or without fosbretabulin in patients with ATC.
Patients were randomly assigned in a 2:1 ratio to 6 cycles of paclitaxel 200 mg/m(2) followed by carboplatin AUC 6 on day 1 every 3 weeks (CP), or these drugs were given on day 2 after fosbretabulin 60 mg/m(2) (CP/fosbretabulin) on days 1, 8 and 15. After 6 cycles, patients on the fosbretabulin arm without progression could continue to receive fosbretabulin on days 1 and 8 of a 3-week schedule until progression. The primary end point was overall survival (OS).
Eighty patients were assigned (planned, 180) when enrollment was stopped due to rarity of disease and very low accrual. Median OS was 5.2 months [95% confidence interval (CI) 3.1, 9.0] for the CP/fosbretabulin arm (n=55; hazard ratio 0.73 [95% CI 0.44, 1.21]) and 4.0 months [95% CI 2.8, 6.2] for the CP arm (n=25; p=0.22 [log rank test]). One-year survival for CP/fosbretabulin versus CP was 26% versus 9%, respectively. There was no significant difference in progression-free survival between the two arms. Grade 1-2 hypertension and grade 3-4 neutropenia were more common with CP/fosbretabulin. There were no significant adverse cardiovascular side effects.
Although the study did not meet statistical significance in improvement in OS with the addition of fosbretabulin to carboplatin/paclitaxel, it represents the largest prospective randomized trial ever conducted in ATC. The regimen is well tolerated, with AEs and deaths primarily related to ATC and disease progression.
间变性甲状腺癌（ATC）是一种罕见的高度血管化肿瘤，预后极差。我们对 ATC 患者进行了卡铂/紫杉醇联合或不联合福司替尼丁治疗的开放性、随机 2:1 研究。
患者以 2:1 的比例随机分配接受 6 个周期的紫杉醇 200mg/m2 联合卡铂 AUC6 于第 1 天（CP 方案），或在福司替尼丁 60mg/m2（第 1、8 和 15 天）给药后的第 2 天给予这些药物（CP/福司替尼丁）。6 个周期后，福司替尼丁组中无进展的患者在疾病进展前可继续在每 3 周的方案中接受福司替尼丁治疗，于第 1 和第 8 天用药。主要终点是总生存期（OS）。
当由于疾病罕见且入组率极低而停止入组时，共纳入 80 例患者（计划纳入 180 例）。CP/福司替尼丁组的中位 OS 为 5.2 个月[95%置信区间（CI）3.1，9.0]（n=55；风险比 0.73[95%CI 0.44，1.21]），CP 组的中位 OS 为 4.0 个月[95%CI 2.8，6.2]（n=25；p=0.22[对数秩检验]）。CP/福司替尼丁组和 CP 组的 1 年生存率分别为 26%和 9%。两组之间无进展生存期无显著差异。CP/福司替尼丁组更常见 1-2 级高血压和 3-4 级中性粒细胞减少。无明显心血管不良事件。
尽管添加福司替尼丁未能显著提高卡铂/紫杉醇治疗的 OS，但该研究代表了 ATC 有史以来最大的前瞻性随机试验。该方案耐受性良好，AE 和死亡主要与 ATC 和疾病进展有关。
