Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation.
Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation.
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DOI：
10.1158/1078-0432.ccr-10-0994
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Martins RG
中科院分区：
文献类型：
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作者：
Carr LL;Mankoff DA;Goulart BH;Eaton KD;Capell PT;Kell EM;Bauman JE;Martins RG
我们进行了一项II期研究，以评估舒尼替尼连续给药在FDG-PET缺乏、碘难治性、高分化甲状腺癌（WDTC）和甲状腺髓样癌（MTC）患者中的疗效，并评估FDG-PET的早期反应。患者患有转移性、碘难治性WDTC或MTC伴FDG-PET avid疾病。舒尼替尼以37.5 mg/天连续给药。主要终点是根据RECIST标准的反应率。次要终点包括毒性、总生存期（OS）和疾病进展时间（TTP）。我们对治疗7天后的FDG-PET反应进行了探索性分析。35例患者入组（7例MTC;28例WDTC），33例患者可评价疾病缓解。主要终点，根据RECIST标准的客观缓解率为11例患者，31%（95% CI：16%-47%）。完全缓解1例（3%），部分缓解10例（28%），病情稳定16例（46%）。在17%（6例患者）中观察到疾病进展。中位TTP为12.8个月（95%CI，8.9个月-未达到）。对22例患者进行了重复FDG-PET，对于RECIST缓解、稳定和疾病进展的患者，平均SUV的中位百分比变化分别为− 11.7%、− 13.9%和8.6%。应答类别之间的差异具有统计学显著性（p=0.03）。最常见的毒性包括：疲劳（11%）、中性粒细胞减少症（34%）、手/足综合征（17%）、腹泻（17%）和白细胞减少症（31%）。1例接受抗凝治疗的患者死于胃肠道出血。舒尼替尼持续给药对碘难治性WDTC和MTC患者有效。需要进一步研究。
We conducted a phase II study to assess the efficacy of continuous dosing of sunitinib in patients with FDG-PET avid, iodine refractory, well-differentiated thyroid carcinoma (WDTC) and medullary thyroid cancer (MTC), and to assess for early response per FDG-PET. Patients had metastatic, iodine-refractory WDTC or MTC with FDG-PET avid disease. Sunitinib was administered at 37.5 mg daily on a continuous basis. The primary end-point was response rate per RECIST criteria. Secondary end-points included toxicity, overall survival (OS), and time to progression (TTP). We conducted an exploratory analysis of FDG-PET response after 7 days of treatment. Thirty-five patients were enrolled (7 MTC;28 WDTC), and 33 patients were evaluable for disease response. The primary endpoint, objective response rate per RECIST criteria, was 11 patients, 31% (95% CI: 16% to 47%). There was one complete response (3%),10 partial responses (28%), and 16 patients (46%) with stable disease. Progressive disease was seen in 17% (6 patients). The median TTP is 12.8 months (95%CI, 8.9 months – not reached). Repeat FDG-PET was performed on 22 patients, the median percent change in average SUVs was −11.7%, −13.9%, and 8.6% for patients with RECIST response, stable, and progressive disease respectively. Differences between response categories were statistically significant (p=0.03). The most common toxicities seen included: fatigue (11%), neutropenia (34%), hand/foot syndrome (17%), diarrhea (17%), and leukopenia (31%). One patient on anticoagulation died of gastrointestinal bleeding. Continuous administration of sunitinib was effective in patients with iodine refractory WDTC and MTC. Further study is warranted.