Single-Dose Prevention or Short-Term Treatment with Fibroblast Growth Factor-20 (CG53135-05)Reduces the Severity and Duration of Oral Mucositis.

Oral mucositis (OM) is a treatment-limiting condition associated with myelosupressive chemotherapy and radiation therapy. The objective of this study was to evaluate the activity of recombinant human fibroblast growth factor-20 (FGF-20 or CG53135-05) in the prevention and treatment of OM in experimental animals. Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60 mg/kg) on days -4 and -2, followed by targeted irradiation with 30 Gy on day 0.

A phase I study of CR002, a fully-human monoclonal antibody against platelet-derived growth factor-D.

Objective: To investigate the safety, pharmacokinetics (PK), binding activity and immunogenicity of CR002, a human monoclonal antibody (mAb) directed against platelet-derived growth factor-D (PDGF-D), administered as a single intravenous (i.v.) infusion over a range of doses.

Safety and tolerability of velafermin (CG53135-05) in patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplant.

Goals Of Work: The objective of this study was to evaluate the safety and tolerability of velafermin in patients at risk of developing severe oral mucositis (OM) from chemotherapy.

Materials And Methods: This study was a single-center, open-label, single-dose escalation, phase I trial in patients undergoing high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant (PBSCT). Velafermin was administered 24 h after stem cell infusion as a single intravenous dose infused over 15 min.

Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB.

Purpose: To investigate the pharmacological properties of the CR011-vcMMAE fully human antibody-drug conjugate (ADC), such as dose titrations, quantitation of the time (days) to complete regression, pharmacokinetics, and schedule dependency. Our prior study characterized a fully human antibody to GPNMB covalently linked to monomethylauristatin E, CR011-vcMMAE, and further demonstrated cell surface staining of melanoma lines susceptible to the immunoconjugate's cytotoxicity (Clin Cancer Res 2005; 12(4): 1373-1382).

Methods: The human SK-MEL-2 and SK-MEL-5 melanoma xenografts were used in athymic mice to assess anti-tumor efficacy.

Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses.

Aim: The use of acetylcholinesterase inhibitors for the treatment of comorbid Alzheimer's disease in Parkinson's disease (PD) patients stabilized on a levodopa regimen may potentially disrupt cholinergic balance. This randomized, double-blind, crossover study investigated the safety of, and possible drug-drug interaction between, donepezil HCl and levodopa/carbidopa.

Methods: Twenty-five patients with PD who were taking physician-optimized doses of levodopa/carbidopa (with daytime dosing intervals of 4-8 h) were administered once-daily doses of either donepezil HCl (5 mg) or placebo for 15 days, in two treatment periods, separated by a washout of at least 2 weeks.

Integrated acidity and rabeprazole pharmacology.

Background: Integrated gastric and oesophageal acidity can be calculated from measurements of gastric and oesophageal pH and used to quantify gastric and oesophageal acidity over time. Rabeprazole is a new proton pump inhibitor that is effective in treating gastro-oesophageal reflux disease (GERD).

Aim: To use measurement of integrated gastric and oesophageal acidity to determine the onset, duration and overall effect of rabeprazole in subjects with GERD.

Review article: rabeprazole-based therapy in Helicobacter pylori eradication.

Rabeprazole's favourable pharmacodynamic profile is a result of its rapid onset and its 24-h control of gastric parietal secretion. These qualities, and its antimicrobial properties, make it particularly effective in the treatment of Helicobacter pylori (H. pylori), which is a short course of treatment compared to other conditions treated with proton pump inhibitors.

Rabeprazole for the prevention of recurrent erosive or ulcerative gastro-oesophageal reflux disease. Rabeprazole Study Group.

Objectives: To evaluate the efficacy and tolerability of rabeprazole 10 mg and 20 mg versus placebo for the prevention of endoscopically demonstrable relapse in patients previously diagnosed with erosive or ulcerative gastro-oesophageal reflux disease (GORD) who had no oesophageal erosions or ulcerations at study entry. The study also assessed the effectiveness of rabeprazole in preventing GORD symptom recurrence and reductions in quality of life.

Design/methods: The trial used a multicentre, randomized, double-blind, parallel-group design and enrolled 288 male and female outpatients of > or =18 years of age.

Dolasetron for the prevention of postoperative nausea and vomiting following outpatient surgery with general anaesthesia: a randomized, placebo-controlled study. The Dolasetron PONV Prevention Study Group.

In a multicentre, randomized, double-blind, placebo-controlled dose-ranging study, 1030 patients undergoing outpatient surgery with general anaesthesia received i.v. dolasetron mesylate (12.

Single- and multiple-dose pharmacokinetics of oral dolasetron and its active metabolites in healthy volunteers: part 2.

The single- and multiple-dose pharmacokinetics and dose-proportionality of oral dolasetron and its active metabolites over the therapeutic dose range was investigated in 18 healthy men. In an open-label, randomized, complete three-way crossover design, each subject received three separate doses: 50, 100, and 200 mg doses of dolasetron mesylate solution given orally. Each dose was administered on the morning of Days 1 and 3-7 during each of the three treatment periods.

Intravenous pharmacokinetics and absolute oral bioavailability of dolasetron in healthy volunteers: part 1.

In this first part of a two-part investigation, the intravenous dose proportionality of dolasetron mesylate, a 5-HT3 receptor antagonist, and the absolute bioavailability of oral dolasetron mesylate were investigated. In an open-label, randomized, four-way crossover design, 24 healthy men between the ages of 19 and 45 years received the following doses: 50, 100, or 200 mg dolasetron mesylate administered by 10-min intravenous infusion or 200 mg dolasetron mesylate solution administered orally. Serial blood and urine samples were collected for 48 h after dosing.

Rationale for the use of a single fixed intravenous dolasetron dose for the prevention of cisplatin-induced nausea and vomiting. Pooled analysis of 14 clinical trials.

Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents chemotherapy-induced and postoperative nausea and vomiting. For the majority of patients in intravenous dolasetron trials for chemotherapy-induced nausea and vomiting, dosing has been based on body weight (mg/kg). The approved weight-based dose is 1.

Oral dolasetron mesylate for prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study. The Oral Dolasetron PONV Prevention Study Group.

Study Objective: To examine the safety and effectiveness of a range of single oral doses of dolasetron mesylate for the prevention of postoperative nausea and vomiting.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: 32 hospitals.

The effect of food on the bioavailability of dolasetron mesylate tablets.

Anzemet (dolasetron mesylate) is being developed for the prevention of chemotherapy-induced emesis and postoperative nausea and vomiting. Twenty-four healthy male subjects were orally dosed with dolasetron mesylate, 200 mg, after either an overnight fast or a high-fat breakfast. The ratio of the mean area under the plasma concentration-time curve of the reduced active metabolite (MDL 74,156) to infinity (AUC(0-infinity)) values in fed compared to fasting subjects was 86.

Pharmacokinetics of dolasetron after oral and intravenous administration of dolasetron mesylate in healthy volunteers and patients with hepatic dysfunction.

In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III).

Effect of infusion rate on the pharmacokinetics and tolerance of intravenous dolasetron mesylate.

Objective: To evaluate the safety, tolerance, and pharmacokinetics of dolasetron mesylate and its active metabolite hydrodolasetron when dolasetron mesylate was administered intravenously at increasing infusion rates.

Design: A double-blind, placebo-controlled, parallel-group study.

Methods: Forty-nine healthy nonsmoking male volunteers were randomly assigned to receive intravenous doses of dolasetron mesylate 100 mg or placebo.

Treatment of postoperative nausea and vomiting with single intravenous doses of dolasetron mesylate: a multicenter trial. Dolasetron Mesylate PONV Treatment Study Group.

Unlabelled: This study was conducted to determine the efficacy and safety of four intravenous (I.V.) doses of dolasetron, an investigational 5-HT3 receptor antagonist, for the treatment of postoperative nausea and/or vomiting (PONV) after outpatient surgery under general anesthesia.

Intravenous dolasetron and ondansetron in prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study.

Background: Intravenous dolasetron mesilate has shown efficacy in the prevention of postoperative nausea and vomiting (PONV) when administered as a single dose prior to emergence from anesthesia. This trial compared intravenous dolasetron and ondansetron for the prevention of PONV when administered at induction of anesthesia.

Methods: This double-blind, placebo-controlled, multicenter trial randomized patients to one of four single IV treatments placebo, 25 or 50 mg dolasetron, or 4 mg ondansetron.

Intravenous dolasetron mesilate in the prevention of postoperative nausea and vomiting in females undergoing gynecological surgery.

Study Objective: To evaluate a range of doses of intravenous (i.v.) dolasetron mesilate, in preventing postoperative nausea and vomiting (PONV).

Randomized, double blind, dose-response trial across four oral doses of dolasetron for the prevention of acute emesis after moderately emetogenic chemotherapy. Oral Dolasetron Dose-Response Study Group.

Background: This double blind parallel group study assessed the acute antiemetic efficacy of four oral doses of dolasetron mesylate in cancer patients receiving their first course of intravenous chemotherapy with doxorubicin and/or cyclophosphamide.

Methods: Patients were randomized to receive 25, 50, 100, or 200 mg of dolasetron mesylate 30 minutes prior to chemotherapy and were monitored for nausea and emetic episodes for the next 24 hours.

Results: Three hundred and nineteen cancer patients at 32 sites completed the study.

Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting.

Purpose: To compare the efficacy, safety, and tolerability of dolasetron mesilate with placebo for the treatment of postoperative nausea and vomiting (PONV).

Methods: In a randomized, multicentre, double-blind, placebo-controlled study 337 adult patients undergoing surgery with general anaesthesia received one of four single, doses of dolasetron mesilate iv (12.5, 25, 50, or 100 mg) or placebo.

Intravenous dolasetron for the prevention of postoperative nausea and vomiting after outpatient laparoscopic gynecologic surgery.

The newer 5-hydroxytryptamine type 3 (5-HT3) antagonists are sometimes considered for routine prophylaxis of postoperative nausea and vomiting (PONV) in high-risk patients. This multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and safety of three single intravenous (IV) doses of dolasetron mesylate salt (12.5, 25, or 50 mg) for the prevention of PONV in 635 females undergoing outpatient laparoscopic gynecologic surgery.

A double-blind, randomized study of two different dosage regimens of intravenous dolasetron in patients receiving high-dose cisplatin chemotherapy.

This study compared the antiemetic efficacy and safety of two different intravenous (i.v.) dolasetron dosing regimens in patients receiving their first course of high-dose (> or = 80 mg/m2) cisplatin.

Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy. Oral Dolasetron Dose Response Study Group.

Purpose: This double-blind, dose-response study was conducted to assess the safety and efficacy of four oral doses of dolasetron mesylate for preventing acute emesis in cancer patients receiving their first course of moderately emetogenic platinum-containing chemotherapy.

Patients And Methods: Patients were randomized to receive a single oral dose of 25, 50, 100, or 200 mg dolasetron 30 minutes before receiving IV carboplatin (275-400 mg/m2)- or cisplatin (20-50 mg/m2)-containing chemotherapy, then monitored for nausea and vomiting for 24 hours.

Results: Three hundred seven cancer patients from 32 sites completed the study.