1 Department of Pediatrics, Division of Hematology/Oncology, Texas Children's Cancer Center; Division of Endocrinology; Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.
2 Department of Pediatrics, Division of Endocrinology, Alberta Children's Hospital , Calgary, Alberta, Canada .
Thyroid. 2018 Nov;28(11):1450-1454. doi: 10.1089/thy.2018.0064. Epub 2018 Oct 16.
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy in children and adolescents. Infrequently, children with PTC may present with or develop disease not amenable to surgery or radioactive iodine (RAI), and systemic therapy may be an option. Lenvatinib is an oral tyrosine kinase inhibitor that is approved by the Food and Drug Administration for the treatment of adults with locally recurrent or metastatic, progressive, RAI-refractory well-differentiated thyroid carcinoma. The effect of lenvatinib in children with PTC has not been reported.
Three children with metastatic PTC not amenable or refractory to RAI who responded to lenvatinib are reported. All of them developed respiratory distress requiring oxygen caused by extensive bilateral metastatic pulmonary disease. The first patient is a 14-year-old female who was initially treated with sorafenib for extensive PTC not amenable to upfront surgery or RAI. She had progressive pulmonary disease after five months, and was subsequently treated with oral lenvatinib (14 mg/m/day). She was weaned to room air after eight weeks. The second patient is a 15-year-old male who was treated with lenvatinib (14 mg/m/day) for iodine non-avid diffuse pulmonary disease after initial total thyroidectomy and cervical lymph node dissection. He was weaned off oxygen in six weeks. The third patient is a five-year-old male who was treated with lenvatinib (14 mg/m/day) for pulmonary disease progression 24 months after treatment with total thyroidectomy, cervical lymph node dissection, and RAI treatment. He was weaned off oxygen one day after starting lenvatinib. Two of the patients required dose adjustments secondary to proteinuria. Otherwise, all patients tolerated lenvatinib well. The first two patients remained clinically stable on lenvatinib 23 months and 11 months after initiation of therapy, respectively, and the third patient transitioned to a tumor-specific targeted therapy after one month.
Three pediatric patients are reported with metastatic PTC not amenable or refractory to RAI who achieved a response on lenvatinib.
Lenvatinib therapy is well tolerated and demonstrated clinical activity in children with advanced PTC. Lenvatinib should be considered in children with PTC that is refractory or not amenable to conventional management.
甲状腺癌（PTC）是儿童和青少年中最常见的甲状腺恶性肿瘤。少数 PTC 患儿可能表现出或发展为手术或放射性碘（RAI）不可治疗的疾病，全身治疗可能是一种选择。仑伐替尼是一种口服酪氨酸激酶抑制剂，已被美国食品和药物管理局批准用于治疗局部复发性或转移性、进行性、RAI 难治性分化良好的甲状腺癌的成人。仑伐替尼在 PTC 患儿中的疗效尚未报道。
报道了 3 例转移性 PTC 患儿，这些患儿对 RAI 不可治疗或耐药，并对仑伐替尼有反应。所有患儿均因广泛双侧转移性肺疾病导致呼吸窘迫，需要吸氧。第 1 例患者为 14 岁女性，最初接受索拉非尼治疗，因广泛的 PTC 不能进行手术或 RAI 治疗。5 个月后，她的肺部疾病进展，随后接受口服仑伐替尼（14mg/m/天）治疗。8 周后，她成功撤机。第 2 例患者为 15 岁男性，初始接受甲状腺全切除术和颈部淋巴结清扫术，碘不摄取弥漫性肺疾病后，接受仑伐替尼（14mg/m/天）治疗。6 周后，他成功撤机。第 3 例患者为 5 岁男性，甲状腺全切除术、颈部淋巴结清扫术和 RAI 治疗后 24 个月，肺部疾病进展，开始接受仑伐替尼（14mg/m/天）治疗。仑伐替尼治疗 1 天后，他成功撤机。有 2 例患者因蛋白尿而需要调整剂量。否则，所有患者均耐受仑伐替尼良好。前 2 例患者分别在接受治疗 23 个月和 11 个月后仍保持临床稳定，第 3 例患者在接受治疗 1 个月后转为肿瘤特异性靶向治疗。
报道了 3 例转移性 PTC 患儿，这些患儿对 RAI 不可治疗或耐药，对仑伐替尼有反应。
仑伐替尼治疗儿童晚期 PTC 耐受良好，具有临床活性。对于对常规治疗耐药或不耐受的 PTC 患儿，应考虑仑伐替尼治疗。
