Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study.

This open-label, single-arm phase II study examined efficacy, safety, pharmacokinetics, and biomarkers of histone deacetylase (HDAC) inhibitor resminostat in patients with relapsed or refractory Hodgkin lymphoma. Thirty-seven heavily pretreated patients received 600 (19 patients) or 800 mg (18 patients) oral resminostat daily for the initial 5 days of 14-day treatment cycles. Objective response rate (ORR) (primary) was 34% reaching disease control in 54% patients. Most patients (69%) showed reduced tumor size and reduced [18F]-FDG uptake in target lesions (71%). Median progression-free survival (PFS) was 2.3 months (95%CI [1.3; 3.3]) and median overall survival (OS) was 12.5 months (95%CI [9.6; 18.6]). Patients who responded or stabilized under resminostat had a 10-month longer OS than patients who progressed. Efficacy assessment, pharmacodynamics, and exploratory biomarker results followed plasma levels, showed target engagement and epigenetic modulations. Common drug-related adverse events (AEs) were nausea, vomiting, anemia, thrombocytopenia, and fatigue, mainly grade 1 or 2.

The diagnostic role of 68Ga-DOTATATE PET/CT in the detection of neuroendocrine tumours.

BACKGROUND: Positron emission tomography (PET) combined with computer tomography (CT) using (68)Ga-DOTATATE is a promising method for the evaluation of patients with recognised or suspected neuroendocrine tumours (NET). The aim of this study was to assess the diagnostic value of (68)Ga-DOTATATE PET/CT in the visualisation of the expression of somatostatin receptors (SSTR) and identification of new lesions. MATERIAL AND METHODS: Between December 2009 and January 2011 ninety-seven patients with confirmed (88 cases) or suspected (9 cases) NET underwent (68)Ga DOTATATE PET/CT. The primary, confirmed or suspected, NET localizations were: GEP tumours--71 patients; medullary thyroid carcinoma--4 patients; cancer of an unknown primary--14 patients; and NET in other localisations--8 patients. PET/CT acquisitions were performed using standard techniques, 45 to 60 minutes after the intravenous injection of 111-185 MBq (68)Ga-DOTATATE. RESULTS: (68)Ga-DOTATATE PET/CT detected the presence of lesions demonstrating the somatostatin receptor affinity in 50 of the 97 patients (51.5%) and was negative in 47 patients (48.5%). Among 14 patients with metastatic unknown primary cancer, in 5 patients (45.5%) the primary tumour site was identified, and in 4 patients with medullary thyroid cancer distant metastases with SSTR expression were localized in only one patient. CONCLUSIONS: Our findings confirm the diagnostic role of (68)Ga-DOTATATE PET/CT as an accurate method of identifying primary tumours and distant metastases. It provides information on tumour cell receptors status, which has a significant bearing on planning target radionuclide therapy. Overall, (68)Ga-DOTATATE PET/CT can be used in staging, re-staging, and in regular follow up of oncology patients.