Sun Min Lim1, Woong Youn Chung2, Kee-Hyun Nam2, Sang-Wook Kang2, Jae Yun Lim3, Hoon-Gu Kim4, Seong Hoon Shin5, Jong-Mu Sun6, Seong-Geun Kim7, Joo-Hang Kim1, Chan Woo Kang8, Hye Ryun Kim9, Byoung Chul Cho10. 1. Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Gangnam Severance Hospital, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang Regional Cancer Center, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea. 5. Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea. 6. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 7. Division of Hematology-Oncology, Pusan National University Yangsan Hospital, Busan, Republic of Korea. 8. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Republic of Korea. 9. Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: NOBELG@yuhs.ac. 10. Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: cbc1971@yuhs.ac.
Abstract
BACKGROUND: This phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancer patients. PATIENTS AND METHODS: Patients with advanced thyroid cancer that was refractory or not appropriate for (131)I received dovitinib orally, 500mg once daily for five consecutive days, followed by a 2-day rest every week. The primary end-point was objective response rate. Secondary end-points were progression-free survival (PFS), overall survival (OS), duration of response, changes in tumour markers and safety. RESULTS: Between January 2013 and October 2014, a total of 40 patients were enrolled. There were 23 (57.5%) papillary thyroid cancer, 12 (30%) medullary thyroid cancer and 5 (12.5%) follicular thyroid cancer patients. One patient had withdrawn consent before the administration of dovitinib. The overall response rate was 20.5% (8/39) and disease control rate was 69.1% (26/39). Median PFS was 5.4 months (95% confidence interval (CI), 2.0-8.8) and median OS was not reached with 8.4 months follow-up duration. Common treatment-related adverse events were diarrhoea (53.8%), anorexia (35.8%), vomiting (25.6%), fatigue (23%) and nausea (20.5%), most of which were grade 1 or 2. There were no grade 4 events or treatment-related deaths. Dose interruption occurred in 12 (30.7%) patients, and 19 (48.7%) patients experienced dose reduction due to adverse events. CONCLUSIONS: Dovitinib has a modest activity with manageable toxicity in locally advanced or metastatic thyroid cancer.
BACKGROUND: This phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancerpatients. PATIENTS AND METHODS: Patients with advanced thyroid cancer that was refractory or not appropriate for (131)I received dovitinib orally, 500mg once daily for five consecutive days, followed by a 2-day rest every week. The primary end-point was objective response rate. Secondary end-points were progression-free survival (PFS), overall survival (OS), duration of response, changes in tumour markers and safety. RESULTS: Between January 2013 and October 2014, a total of 40 patients were enrolled. There were 23 (57.5%) papillary thyroid cancer, 12 (30%) medullary thyroid cancer and 5 (12.5%) follicular thyroid cancerpatients. One patient had withdrawn consent before the administration of dovitinib. The overall response rate was 20.5% (8/39) and disease control rate was 69.1% (26/39). Median PFS was 5.4 months (95% confidence interval (CI), 2.0-8.8) and median OS was not reached with 8.4 months follow-up duration. Common treatment-related adverse events were diarrhoea (53.8%), anorexia (35.8%), vomiting (25.6%), fatigue (23%) and nausea (20.5%), most of which were grade 1 or 2. There were no grade 4 events or treatment-related deaths. Dose interruption occurred in 12 (30.7%) patients, and 19 (48.7%) patients experienced dose reduction due to adverse events. CONCLUSIONS:Dovitinib has a modest activity with manageable toxicity in locally advanced or metastatic thyroid cancer.
Authors: Haitham AlRabiah; Adnan A Kadi; Haya I Aljohar; Mohamed W Attwa; Nasser S Al-Shakliah; Sabry M Attia; Gamal Ae Mostafa Journal: Drug Des Devel Ther Date: 2020-01-28 Impact factor: 4.162