进展性碘难治性分化型甲状腺癌患者阿帕替尼治疗后血清学与影像学指标变化

Follow-up study on biochemical and structural response in progressive radioactive iodine-refractory differentiated thyroid cancer patients treated with apatinib

目的:评估阿帕替尼对于局部进展性碘难治性分化型甲状腺癌(radioactive iodine-refractory differentiated thyroid cancer,RAIR-DTC)中位随访7.9个月后的治疗效果。方法:随访中国医学科学院北京协和医院自2016年3月至2016年6月入组阿帕替尼治疗RAIR-DTC临床实验的受试者10例,从血清生化角度,甲状腺球蛋白(thyroglobulin,Tg)、甲状腺球蛋白抗体(thyroglobulin antibody,Tg-Ab)及影像学角度,靶病灶长度(target lesions,TL)观察阿帕替尼疗效及相关性,总结随访期间的不良事件(adverse event,AE)。结果:中位随访时间为7.9个月,在平均服用阿帕替尼6周内Tg呈快速下降趋势,平均下降60%,最大可达90%,提示该药物血清学疗效反应迅速,此后呈现稳定趋势,但停药3~14天即可观察到Tg的反弹趋势,升幅波动在4%~135%;TL在服用阿帕替尼平均8周内呈快速下降趋势,平均下降40%,最大可达60%,提示该药物快速的影像学疗效反应,此后呈稳定趋势,受停药影响不明显;Tg周变化速率(Tgvn)和TL周变化速率(TLvn)呈正相关[TLvn=0.17×Tgvn+0.50(r=0.56,P<0.05)];受试者因不良反应均有不同程度的剂量下调,剂量调整后AE于3~14天缓解,下调剂量至250 mg/d仍能有效控制病情。结论:阿帕替尼治疗进展性RAIR-DTC具有快速、持久的血清学及影像学反应,Tgvn和TLvn呈正相关,且Tg较TL更为敏感,应作为RAIR-DTC靶向治疗评估的客观指标。

Objective： To evaluate the biochemical and structural changes of apatinib in patients with progressive radioactive iodine-refractory differentiated thyroid cancer （RAIR-DTC）. Methods： The participants （n=10） were followed up since March 2016. Treatment effect was evaluated in using both biochemical [thyroglobulin （Tg） and thyroglobulin antibody （Tg-Ab）] and structural responses （target lesions, TL）. Adverse events were also recorded over time. Results： The median follow-up was 7.9 months. The Tg level declined rapidly within 6 weeks after apatinib treatment, and the average decline ranged from 60% to 90%, indicating the immediate biochemical response of apatinib in progressive RAIR-DTC. The Tg level tended to stabilize thereafter. However, the Tg level rebounded by 4% - 135% when withdrawal was performed for 3 - 14 days. The number of TLs decreased rapidly within 8 weeks, and the average decreased ranged from 40% to 60%, indicating the presence of rapid structural responses. Thereafter, the number of TLs continued to stabilize. TLs, in contrast to Tg, were not significantly affected by drug withdrawal. The rate of change in Tg （Tgvn） was positively correlated with the rate of change in TL （TLvn） [TLvn=0.17×Tgvn＋0.50 （r=0.56, P〈0.05）]. The apatinib dose was adjusted due to adverse events, which could be relieved after 3 to 14 days of withdrawal. Apatinib can effectively control the disease even at a reduced dose of 250 mg/d. Conclusion： Apatinib treatment showed a fast and sustainable biochemical and structural responses. Tg could be regarded as an objective indicator. Tgvn is positively correlated with TLvn, and the response of Tg is more sensitive than that of TLs.