Intermittent versus continuous administration of pazopanib in progressive radioiodine refractory thyroid carcinoma: Final results of the randomised, multicenter, open-label phase II trial PAZOTHYR.

INTRODUCTION: Multikinase inhibitor (MKI) treatments have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC), but most patients experienced substantial adverse effects. This randomised multicentric study investigated intermittent versus continuous pazopanib administration. PATIENTS AND METHODS: The PAZOTHYR study included RAIR-TC patients with progressive disease in the last 12 months, who may have received one prior MKI. RAIR-TC patients received pazopanib for 6 months, and patients with stable disease or tumour response were randomly assigned (1:1) to receive continuous (CP) or intermittent (IP) pazopanib until progression. The primary end-point was time to treatment failure (TTF) defined as the time from randomisation to permanent discontinuation of pazopanib, due to any cause. One hundred randomised patients were needed to demonstrate an increase from 50% (CP) to 70% (IP) (hazard ratio (HR) 0.515, 80% power) in the rate of patients still under treatment 6 months (6m-SuT) post-randomisation. Secondary end-points included the overall response rate (ORR), progression-free survival (PFS) under pazopanib and safety. RESULTS: RAIR-TC patients (168) enrolled from June 18, 2013 to January 16, 2018, received 6-month pazopanib treatment and showed 35.6% (95% CI 28.2-43.6) best response rate and 89.4% (83.5-93.7) disease control rate. One hundred patients were randomised (IP:50; CP:50). With a median follow-up of 31.3 months, median TTF was not statistically different between arms (IP:14.7, 95% confidence interval (CI) 9.3-17.4; CP:11.9, 95% CI 7.5-15.6) months (HR 0.79, 0.49-1.27). 6m-SuT rates were similar (IP:80% 66.0-88.7%; CP:78% 63.8-87.2%). Median PFS under pazopanib were not statistically different (IP:5.7 4.8-7.8; CP: 9.2 7.3-11.1) months (HR 1.36, 0.88-2.12). Pazopanib-related adverse events grade 3-4 occurred in 36 (IP: 19, 38%; CP: 17, 34%) randomised patients. Seven pazopanib-related deaths occurred. CONCLUSIONS: Intermittent administration of pazopanib did not demonstrate significant superiority in efficacy or tolerance compared with continuous treatment. An intermittent administration scheme cannot be recommended outside clinical trials. This study was registered with ClinicalTrial.gov, number NCT01813136.

Continuous glucose monitoring and hypoglycemia unawareness in type 1 diabetes: a pilot study.

BACKGROUND: Looking for strict normoglycemia in type 1 diabetes increases the risk of hypoglycemia, exposing to hypoglycemia unawareness. It has been shown that the early correction of hypoglycemia can help recovering the perception of hypoglycemia. The purpose of this prospective study was to assess the value of sensor-augmented insulin-pump therapy to treat hypoglycemia unawareness. METHODS: Eleven patients with type 1 diabetes and partial or total hypoglycemia unawareness received sensor-augmented insulin-pump therapy combined to the low blood glucose-suspend feature (Paradigm® Veo™ pump and Enlite® sensors) for three months. RESULTS: Eighty per cent of the patients improved their hypoglycemia unawareness with an increase in the hypoglycemia perception threshold of 31 mg/dL as evaluated by blinded continuous glucose monitoring. These results were correlated to a self-assessment quiz evaluation. Results were sustained at six months (three months after patients stopped using the system). Sensitive neuropathy, untreated hypoglycemia and the area under the curve for hypoglycemia events were associated with less chance of recovery. These devices were globally considered by the patients as simple to use, with no major disadvantages and only a single withdrawal occurred. CONCLUSIONS: Sensor-augmented insulin-pump therapy should be considered as a possible treatment of hypoglycemia unawareness.

Incidental Detection of Oxyphilic Papillary Thyroid Carcinoma by 18F-Fluorocholine PET/CT.

A 70-year-old man with prostate cancer and increased prostate-specific antigen level of 55 ng/mL underwent staging F-fluorocholine PET/CT, which demonstrated the primary prostate tumor and a focal area corresponding to a 2-cm hypodense nodule in the left thyroid lobe. Fine-needle aspiration and subsequent total thyroidectomy with central lymph node dissection showed an oxyphilic papillary thyroid carcinoma and a medullary microcarcinoma. Oxyphilic tumors represent a significant proportion of the few case reports of incidental focal thyroid fluorocholine thyroid uptake.