A phase I study of pazopanib in combination with escalating doses of (131)I in patients with well-differentiated thyroid carcinoma borderline refractory to radioiodine

OBJECTIVE: This trial was conducted to evaluate the ability of pazopanib to overcome therapeutic (131)I resistance. MATERIALS, METHODS AND PATIENTS: This phase 1 trial assesses the combination of pazopanib and escalating doses of radioiodine ((131)I) in patients with recurrent or metastatic thyroid cancer that are borderline or relatively iodine refractory. Radioiodine uptake scans were assessed post therapy and compared to historical pre-treatment scans. Patients underwent FDG PET/CT before and after the initial pazopanib treatment to identify the impact of pazopanib on the cancer prior to (131)I therapy. RESULTS: A dose limiting toxicity (cardiac arrhythmia and grade 3 fatigue) in the first patient in the first cohort prompted expansion to a total of 6 patients. Additional grade 3–4 hematologic toxicity and low accrual in the expanded cohort led to the decision not to pursue further study of the regimen. In patients with measurable disease 4/5 (80%) achieved stable disease. Median progression free survival was 6.7 months. At 3 years of follow up, one patient died due to progressive disease, two are being treated with systemic therapy and 3 continue without requiring subsequent therapy at 15, 27 and 35 months from the last dose of pazopanib. There was no convincing impact of pazopanib on iodine uptake in scans performed pre- and post-therapy compared to scans from historical (131)I treatments without pazopanib. CONCLUSION: Despite a suggestion of therapeutic efficacy, combined pazopanib and (131)I resulted in increased toxicity. There was no convincing evidence that the administration of pazopanib improved iodine uptake or retention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01413113