Palifermin for oral mucositis in the high-dose chemotherapy and stem cell transplant setting: the Royal Adelaide Hospital Cancer Centre experience

Goals of work the aim of this paper was to review the initial use of Palifermin(rHu-KGF1) in a single institution, for the prevention of oral mucositis in high-dose chemotherapy and stem cell transplantation.Methods the case records of the first five patients treated with Palifermin at the Royal Adelaide Hospital Cancer Centre were reviewed, and incidence,severity and duration of the oral mucositis were recorded, as well as demographics and toxicities.Results two of the five patients developed grade 4 mucositis, and the remaining three patients developed grade 2 mucositis. Palifemin was well tolerated with only one patient developing a rash.Conclusions the severity of oral mucositis was less than would be expected in these patients without anti-mucositis therapy. Palifermin was well tolerated. Obviously this single institution report is from a very small cohort of patients, but it is encouraging for the ease of use of this drug in the future.     

A Comprehensive Map of CNS Transduction by Eight Recombinant Adeno-associated Virus Serotypes Upon Cerebrospinal Fluid Administration in Pigs

Cerebrospinal fluid administration of recombinant adeno-associated viral (rAAV) vectors has been demonstrated to be effective in delivering therapeutic genes to the central nervous system (CNS) in different disease animal models. However, a quantitative and qualitative analysis of transduction patterns of the most promising rAAV serotypes for brain targeting in large animal models is missing. Here, we characterize distribution, transduction efficiency, and cellular targeting of rAAV serotypes 1, 2, 5, 7, 9, rh.10, rh.39, and rh.43 delivered into the cisterna magna of wild-type pigs. rAAV9 showed the highest transduction efficiency and the widest distribution capability among the vectors tested. Moreover, rAAV9 robustly transduced both glia and neurons, including the motor neurons of the spinal cord. Relevant cell transduction specificity of the glia was observed after rAAV1 and rAAV7 delivery. rAAV7 also displayed a specific tropism to Purkinje cells. Evaluation of biochemical and hematological markers suggested that all rAAV serotypes tested were well tolerated. This study provides a comprehensive CNS transduction map in a useful preclinical large animal model enabling the selection of potentially clinically transferable rAAV serotypes based on disease specificity. Therefore, our data are instrumental for the clinical evaluation of these rAAV vectors in human neurodegenerative diseases.     

Economic evaluation of sorafenib in unresectable hepatocellular carcinoma

Background and Aim: A double‐blind, randomized phase III trial of sorafenib in advanced hepatocellular carcinoma demonstrated that sorafenib significantly prolonged overall survival compared to placebo (median overall survival = 10.7 months vs 7.9 months, P < 0.001). Sorafenib is the first and only systemic agent demonstrating survival benefit in these patients. The aim of this study was to assess the cost‐effectiveness of sorafenib versus best supportive care in the treatment of advanced hepatocellular carcinoma in the USA. Methods: A Markov model was developed following time‐to‐progression and survival using phase III trial data. Health effects are expressed as life‐years gained. Resource utilization included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs, expressed in 2007 $US, came from diagnosis‐related groupings, fee schedules, and the Red Book. Costs and effects were evaluated over a patient's lifetime and discounted at 3%. Results: Results are presented as incremental cost/life‐year gained. Deterministic and probabilistic sensitivity analyses were conducted. Life‐years gained were increased for sorafenib compared to best supportive care (mean ± standard deviation: 1.58 ± 0.17 vs 1.05 ± 0.10 life‐years gained/sorafenib patient and best supportive care, respectively). Lifetime total costs were $US40 639 ± $US3052 for sorafenib and $US7 804 ± $US1349 for best supportive care. The incremental cost‐effectiveness ratio was $US62 473/life‐year gained. Conclusions: The economic evaluation indicates that sorafenib is cost‐effective compared to best supportive care, with a cost‐effectiveness ratio within the established threshold that US society is willing to pay (i.e. $US50 000–$US100 000) and significantly lower than alternative thresholds suggested in recent years ($US183 000–$US264 000/life‐year gained, or $US300 000/quality‐adjusted life‐year) in oncology.     

Are There Any Differences Between Nutcracker Esophagus With and Without Reflux?

“Nutcracker esophagus” (NE) is a primary esophageal motor disorder, first described in patients with noncardiac chest pain. In recent years NE has been associated with gastroesophageal reflux disease (GERD). In this study we compare patients with NE with and without GERD, as defined by pHmetry or endoscopy, with respect to clinical, endoscopic, radiologic, and manometric findings. Fifty-two patients with NE were studied. They were divided in two groups: GERD (17–32.6%) and non-GERD (35–67.4%) patients. Females predominated in both groups, with no significant difference in age (p > 0.05). Chest pain was the chief complaint in both groups (p > 0.05). Clinical findings in patients with and without reflux included chest pain (52.9% and 51.4%), dysphagia (58.8% and 42.8%), and heartburn (64.7% and 42.8%), followed by regurgitation, dyspepsia, ear, nose, and throat (ENT) complaints, respiratory symptoms, and odynophagia (p > 0.05). Erosive esophagitis was found in three patients (5.7%). There were no differences between groups in the findings of barium swallow studies and all manometric findings were similar for both groups (p > 0.05). We conclude that there were no differences in patients with NE with or without associated reflux disease. It is important to diagnose reflux properly so patients can be treated adequately.