Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Using jugular bulb oxyhemoglobin saturation to guide onset of deep hypothermic circulatory arrest does not affect post-operative neuropsychological function.

OBJECTIVES: Deep hypothermic circulatory arrest (DHCA) is commonly used during thoracic aortic surgery, and is initiated only after a sufficient degree of cerebral hypothermia is induced. The criteria for initiating DHCA vary among institutions: most centers use temperature criteria, some use electroencephalography, and a minority use jugular bulb oxyhemoglobin saturation SjO(2) criteria. The purpose of this study was to determine whether the use of SjO(2) monitoring to guide the onset of DHCA was associated with better post-operative neuropsychological outcome. METHODS: Sixty-one thoracic aortic surgical patients underwent both pre- and post-operative neuropsychological testing. Patients were divided into three groups: (1) those with SjO(2)> or =95% at DHCA onset; (2) those with SjO(2)<95% at DHCA onset; and (3) those without SjO(2) monitoring. RESULTS: There were no statistically significant differences in the incidence of post-operative decline in neuropsychological function among the three groups of patients. Patients in whom SjO(2) data were used to guide onset of DHCA had lower esophageal and bladder temperatures at that time compared with patients without SjO(2) monitoring. CONCLUSIONS: Monitoring of SjO(2) had no apparent effect upon post-operative neuropsychological outcome, and there were no trends in our small patient cohort suggesting differences that our study was not adequately powered to detect. Use of SjO(2) monitoring was associated with more profound hypothermia prior to DHCA due to more prolonged cooling in attempts to bring the SjO(2) above the 95% threshold. Using our institutional cooling protocol, SjO(2) monitoring does not appear to increase neuroprotection in patients undergoing DHCA for thoracic aortic repairs.     

Astrocyte and microglial motility in vitro is functionally dependent on the hyaluronan receptor RHAMM

RHAMM (Receptor for Hyaluronic Acid Mediated Motility) has been identified as a receptor for the extracellular matrix component hyaluronan (HA) and was recently shown to be essential for the locomotion of normal and transformed peripheral cells. Until now the potential role of RHAMM in the motility of neural-derived cells has not been investigated. Here, we report that cultured primary astrocytes, astrocyte cell lines, and microglia express this receptor and exhibit RHAMM-dependent motility. Immunocytochemical localization of RHAMM showed that it was often present as aggregates at the periphery of cells in contact with one another or concentrated on protruding processes of isolated cells. Glial cells contained 50 and 72 kDa forms of RHAMM, and both of these forms were found to have HA binding capacity. Time lapse imaging of cell locomotion revealed a significant inhibition of motility and process elongation by neutralizing anti-RHAMM antibodies and by peptides corresponding to the HA binding domains of RHAMM. These results demonstrate that RHAMM serves a role in glial cell locomotion in vitro and provide the basis for investigations of the motile behavior of glial cells in vivo after CNS injury.