Pasireotide produced a decrease in UFC levels in 76% of patients with Cushing's disease during the treatment period of 15 d, with direct effects on ACTH release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.

Intoxication with ␥-hydroxybutyric acid (GHB) is associated with coma, seizure, and death; treatment of overdoses is symptomatic. The objectives of this investigation were to characterize the renal clearance and total clearance of GHB in rats and to evaluate potential strategies for increasing the elimination of GHB after drug overdoses. GHB was administered by i.v. infusion at low (108 mg/h/kg), medium (128 mg/h/kg), or high (208 mg/h/kg) doses. Crossover studies were performed under steady-state conditions using the medium dose in the absence or presence of L-lactate, pyruvate, D-mannitol, sodium bicarbonate, or normal saline. GHB in plasma and urine samples was assayed using liquid chromatography-tandem mass spectrometry. Infusion of the low, medium, and high doses of GHB produced steady-state plasma concentrations of 0.22 Ϯ 0.04, 0.43 Ϯ 0.05, and 0.68 Ϯ 0.11 mg/ml. The renal clearance of the medium (51.8 Ϯ 13.0 ml/h/kg) and high (97.1 Ϯ 43.1 ml/h/kg) doses was significantly higher than that of the low dose (14.9 Ϯ 5.1 ml/h/kg), whereas the total clearance values were significantly lower than that of the low dose. The renal clearance was significantly increased by the concomitant administration of L-lactate, pyruvate, D-mannitol, or sodium bicarbonate with GHB but was not altered by normal saline. The total and metabolic clearance values were significantly increased by all treatments except normal saline. Overall, our results indicated that the renal clearance of GHB is dose-dependent, involving capacity-limited reabsorption. Monocarboxylate transport inhibitors, osmotic diuresis using D-mannitol, or the administration of sodium bicarbonate can increase the renal and total clearances of GHB. The approaches used in this investigation may offer potential detoxification strategies for the treatment of GHB overdoses.

Pasireotide is a promising treatment for acromegaly. Larger studies of longer duration evaluating the efficacy and safety of pasireotide in patients with acromegaly are ongoing.

Pasireotide (SOM230) is a novel multireceptor-targeted somatostatin (sst) analog with high binding affinity for sst receptor subtype 1, 2, 3 (sst 1,2,3 ) and sst 5 . Because of this binding profile, pasireotide may offer symptom control in patients with neuroendocrine tumors (NETs) and carcinoid syndrome no longer responsive to octreotide LAR. This was a phase II, open-label, multicenter study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhea/flushing) were inadequately controlled by octreotide LAR. Patients received s.c. pasireotide 150 mg twice daily (bid), escalated to a maximum dose of 1200 mg bid until a clinical response was achieved. Forty-four patients were evaluated for efficacy and 45 for tolerability. Pasireotide 600-900 mg s.c. bid effectively controlled the symptoms of diarrhea and flushing in 27% of patients. Evaluation of tumor response in 23 patients showed 13 with stable disease and ten with progressive disease at study end. The most common drug-related adverse events were nausea (27%), abdominal pain (20%), weight loss (20%), and hyperglycemia (16%) and most were of mild or moderate severity. Pasireotide 600-900 mg s.c. bid was effective and generally well tolerated in controlling the symptoms of carcinoid syndrome in 27% of patients with advanced NET refractory or resistant to octreotide LAR therapy.

BackgroundConcurrent chemoradiotherapy (CCRT) is effective in the treatment of locally advanced cervical squamous cell carcinoma (SCC). However, whether treatment outcomes of cervical adenocarcinoma are equivalent to SCC after CCRT has been a topic of debate.MethodsMedical records of cervical cancer patients treated with definitive radiotherapy or CCRT in our institute from January 2011 to December 2014 were reviewed. Patients were treated with intensity modulated radiation therapy combined with intracavitary brachytherapy. Weekly cisplatin was the first line regimen of concurrent chemotherapy. The treatment outcomes of patients with SCC and adenocarcinoma were compared with a multivariate Cox regression model, and log-rank method before and after propensity score matching (1:1).ResultsA total of 815 patients with stage IB-IVA cervical cancer were included, with 744 patients in the SCC group and 71 patients in adenocarcinoma group. The median follow-up period was 36.2 months (range, 1.0–76.2 months). The 3-year overall survival (OS), disease-free survival (DFS), pelvic control and distant control rates of patients in the SCC group and adenocarcinoma group were 85.2 and 75.4% (p = 0.005), 77.5 and 57.3% (p < 0.001), 89.0 and 74.0% (p = 0.001) and 86.0 and 74.4% (p = 0.011), respectively. After multivariate analysis, histology was an independent factor of OS (p = 0.003), DFS (p < 0.001), pelvic control (p = 0.002) and distant control (p = 0.003). With propensity score matching, 71 pairs of patients were selected. After matching, the OS (p = 0.017), DFS (p = 0.001), pelvic control (p = 0.015) and distant control (p = 0.009) of patients with adenocarcinoma were poorer than those of patients with SCC. In subgroup analysis, patients with adenocarcinoma had significantly worse OS and DFS compared with patients with SCC, regardless of treatment with radiotherapy alone or CCRT.ConclusionThe present study demonstrated that patients with adenocarcinoma of the cervix had poorer OS and DFS than patients with SCC, regardless of treatment with radiotherapy alone or CCRT. New treatment approaches should be considered for cervical adenocarcinoma.