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.     

Use of carbidopa levodopa in a patient with hydrocephalus and frozen movement

While movement disorders are frequently encountered after brain injuries, and may create a host of complicated problems for the clinician, only a few cases of Parkinsonism associated with hydrocephalus have ever been described in the literature. Parkinsonism like syndrome complicating hydrocephalus is a rare disorder, especially when associated with nontumoral aqueductal stenosis. Yet as this case report discusses, hdyrocephalus induced Parkinsonism may be responsive to levodopa-carbidopa administra tion. This report describes a perplexing case of persistent akinesis following corrective surgery for aqueductal stenosis and the subsequent response to levodopa carbidopa administration. We present the case of a 28 year old male with a history of non tumoral aqueductal stenosis diagnosed at age 12. As a child, he underwent a ventriculo peritoneal shunt placement for obstructive hydrocephalus followed by multiple shunt revisions over the next several years. Sixteen years after his initial shunt placement, the patient presented with a decline in mental status. A third ventriculocisternostomy was performed rather than another shunt revision. Following surgery, the patient remained obtunded, and displayed profound hypokinesis, best described as freezing in movement. Upon admission to a rehabiliation unit 2 weeks later, he had made only minimal progress. A SPECT single photon emission computed tomography brain scan revealed decreased basal ganglia perfusion. Levodopa carbidopa therapy was initiated and within 2 weeks, the patient showed improvement in speed of movement, facial expres sion and verbal output. Eight weeks later, the patient could independently complete his basic activities of daily living and demonstrated little, if any, disordered movement. This report illustrates how dopaminergic agents may be useful in cases of hypokinesis following corrective surgery for aqueductal stenosis. SPECT may further aid in the diagnosis and management of Parkinsonism like syndromes in brain injuries.