Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study.

BACKGROUND: A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis. PATIENTS AND METHODS: A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2-4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2-3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2-5 after chemotherapy. RESULTS: Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137 M + D. Day 1 results were similar in both arms. On day 2-5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments. CONCLUSIONS: In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity. CLINICALTRIALSGOV NUMBER: NCT00869310.

Scientific activity and needs among medical oncology units in sicily: a survey of the italian association of medical oncology.

In the era of targeted therapies and combined modalities of treatment, scientific research plays a role of paramount importance in improving knowledge of cancer treatment. The aim of this survey was to review the scientific activity of medical oncology units in Sicily and to analyze their needs and possible pitfalls in order to improve future scientific cooperation.The regional section of the Italian Association of medical Oncology (AIOM) approved this survey in November, 2007. A systematic review of scientific activity produced by medical oncology units in Sicily during the last 5 years has been reviewed. papers dealing with solid tumors reported in the pubmed web site have been included in the analysis. Data were reported as absolute number of published papers and impact factor per medical oncology unit and also as a ratio between global impact factor and the number of personnel working in each single unit to analyze scientific production according to the workforce of each institution.We identified a total of 283 papers reported in pubmed between 2004 and march, 2009. The mean number of publications/unit was 10.9 with a range of 0-50. The mean number of publications/year was 11.7 with a range of 0.2-10. The 15 units included in the impact factor evaluation published 252 papers with a total impact factor of 1014.6 points in 5 years with a mean of 63.4 points per institution and a mean of 4.02 points/paper. However only four medical oncology units reported a cumulative 5-year impact factor >100 points.This survey has shown that a minority of medical oncology units in Sicily is constantly involved in clinical research although at different levels of activity. Overall the percentage of patients enrolled in clinical trials is very low. The main reasons for lack of participation in clinical trials include insufficient medical personnel, the absence of a specifically dedicated research unit inside the medical oncology structures and in some cases lack of research experience and of specific interests in this field.

Metabolic pathways of the anti-hypertensive agent, N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine+ ++ hydrochloride. I. Studies in the rat.

The metabolic fate of a new anti-hypertensive, 1-pyrrolyl pyridazinamine, was studied in male Wistar rats after both p.o. and i.v. administration (1 mg/kg). The compound undergoes rapid metabolism, disappearing from the central compartment with a half-life of about 0.5 h. Plasma concn. of the parent drug and its major metabolite I following i.v. and p.o. administration suggest a route-dependent first-pass metabolism. Ten metabolites were isolated from the urine and identified by u.v., i.r., mass and 1H-n.m.r. spectroscopy. The structure of some was confirmed by 13C-n.m.r. and chemical synthesis. All biotransformations are restricted to the pyrrole ring which undergoes oxidative cleavage followed by a series of chemical rearrangements. A minor pathway leads to the formation of methyl sulphinyl and methyl sulphonyl pyrroles. It is suggested that, as with natural indoles, the pyrrole might be oxidized by a 2,3-dioxygenase. The three major metabolites, I, II and IX, along with two minor ones, VI and VII, were inactive when tested i.v. for antihypertensive activity.