Priya Mahajan1, Jonathan Dawrant2, Albert Kheradpour3, Norma M Quintanilla4, Monica E Lopez5, Robert C Orth6, Ioanna Athanassaki7, Rajkumar Venkatramani1. 1. 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. 2 Department of Pediatrics, Division of Endocrinology, Alberta Children's Hospital , Calgary, Alberta, Canada . 3. 3 Department of Pediatrics, Division of Hematology/Oncology, Loma Linda University , San Bernardino, California. 4. 4 Department of Pathology and Immunology; Division of Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas. 5. 5 Michael E. DeBakey Department of Surgery, Division of Pediatric Surgery; Baylor College of Medicine, Texas Children's Hospital, Houston, Texas. 6. 6 Department of Radiology, Texas Children's Hospital , Houston, Texas. 7. 7 Department of Pediatrics, Division of Endocrinology; Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.
Abstract
BACKGROUND: 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. PATIENT FINDINGS: 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/m2/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/m2/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/m2/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. SUMMARY: Three pediatric patients are reported with metastatic PTC not amenable or refractory to RAI who achieved a response on lenvatinib. CONCLUSION: 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.
BACKGROUND: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. PATIENT FINDINGS: 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/m2/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/m2/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/m2/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. SUMMARY: Three pediatric patients are reported with metastatic PTC not amenable or refractory to RAI who achieved a response on lenvatinib. CONCLUSION: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.
Authors: Laura Fugazzola; Rossella Elisei; Dagmar Fuhrer; Barbara Jarzab; Sophie Leboulleux; Kate Newbold; Jan Smit Journal: Eur Thyroid J Date: 2019-08-28