Pilot Dose Comparison of Apatinib in Chinese Patients With Progressive Radioiodine-Refractory Differentiated Thyroid Cancer

Context: Apatinib has shown overwhelming efficacy in progressive radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) starting at a 750-mg dosing protocol; however, a relatively high incidence of treatment-associated adverse events (TAAEs) was observed, which reduced quality of life and interrupted the treatment. Objectives: To evaluate the efficacy and safety of apatinib with two different dosing schedules [750 or 500 mg once a day (q. d.)] in RAIR-DTC. Participants and Methods: Twenty patients were sequentially recruited to receive apatinib beginning at 750 (n = 10) or 500 (n = 10) mg q. d. Efficacy and safety were compared in each 28-day cycle at the beginning two cycles and every two cycles thereafter. Results: After six treatment cycles, the best disease control rates were 100% for the 750-and 500-mg schedules, respectively, and the best objective response rates were 90.0% and 70.0% (P = 0.58), respectively. The two dosing schedules did not differ regarding greatest reduction in target lesion size (242.7% vs 240.5% for the 750-vs 500-mg schedule, P = 0.48) and thyroglobulin level (282.5% vs 294.3% for the 750-vs 500-mg schedule, P = 0.14). All patients experienced TAAEs, and the two dosing schedules showed similar incidence in TAAEs of grade >= 3 (100% vs 70% for 750 vs 500 mg, P = 0.21). However, the frequency of TAAEs was much higher in the 750-mg schedule (26.8 +/- 6.5 vs 18.1 +/- 6.5 in any grades, P = 0.01; 5.2 +/- 3.0 vs 1.6 +/- 1.3 in grade >= 3, P < 0.01). Conclusion: Within six cycles of follow-up, the 500-mg starting dose protocol might be less toxic than the 750-mg protocol, whereas the efficacy was similar between the two dosages.