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.     

Correlations between follicular fluid steroid analysis and maturity and cytogenetic analysis of human oocytes that remained unfertilized after in vitro fertilization.

OBJECTIVE: Is there any correlation between follicular fluid (FF) steroid levels and the occurrence of cytogenetic abnormalities in unfertilized human oocytes? DESIGN: Cytogenetic analysis was carried out on 397 oocytes, and the steroid content of 104 corresponding FF was analyzed using high-pressure liquid chromatography. Ovarian stimulation was performed by clomiphene citrate and human menopausal gonadotropin (hMG) or by hMG combined with a gonadotropin-releasing hormone agonist (GnRH-a) pretreatment. RESULTS: Oocyte maturity was correlated with an increasing FF progestin content and a significant decrease of androstenedione (A) levels. Chromosomal analysis revealed 84 of all oocytes to be abnormal (polyploid or aneuploid and/or prematurely condensed chromosomes present). In this group, A levels and A to estradiol ratios were significantly higher. Although progestin levels were higher in GnRH-a/hMG cycles, the incidence of oocyte normality was not different between the two stimulation schemes. More abnormal oocytes were found in patients with good sperm morphology. CONCLUSIONS: Oocyte abnormality correlates with higher A levels in the corresponding FF. Oocyte fertilization is also determined by intrinsic oocytic factors other than maturity.     

International round robin tests on the measurement of carbon in diesel exhaust particulates

Object: Diesel soot has been recognized as probably carcinogenic to humans. Elemental carbon (also called black carbon) in soot is considered at the moment as the most significant surrogate to be measured for assessing the exposure to this pollutant. Its analysis is done by combustion in an oven and determination of the CO₂ formed, after elimination of the organic fraction of the soot by heating and/or by solvent extraction. The analysis allows determination of both fractions of the soot: “elemental carbon” (EC) and organic carbon␣(OC). The sum of EC and OC is called TC (total carbon). Method: An informal European coordination group organized two round robin tests on filter samples collected from diluted diesel emissions. The first round (RRT1) was performed on 13 different samples analyzed by ten laboratories. The range of loading was 2.5 to 150 μg/cm² of EC. No evaluation of the precision within laboratories could be made since each laboratory gave only one result per sample. Therefore a second round (RRT2) was organized with two samples and a blank filter sent in several portions to 11 laboratories. It should be stressed that each laboratory used its own method and that no standardization was planned at this stage. Results: Results of RRT1 showed that the coefficient of variation between laboratories decreased with higher loading and was around 10% to 15% for EC above about 20 μg/cm². Dispersion of the results varied and it appeared that the way OC is removed from the soot is probably the most important factor of influence. The correlation between the laboratories was good as a whole but some systematic differences could be detected. Besides the different techniques to remove the organic carbon, the pretreatment of the filter by HCl (either as a vapor or as a solution) to remove the inorganic carbonates (potential interference sources), is probably also a significant factor of influence in the dispersion of the results between laboratories. It is not yet clear from these results whether the “environmental” laboratories give different results from the “occupational” laboratories, but it is clear that their objectives differ since for the “environmentalists”, EC is not a specific marker of diesel immissions, in contrast to the “occupationalists”. Conclusion: It can be concluded that, although significant differences exist between laboratories they can be attributed mainly to the narrow distribution of the results within a single laboratory, and that the overall agreement of the results for EC and TC is fairly good. These results obtained with pure diesel engine emissions, should be complemented by field samples, but they have already achieved relevant findings in the performance of the procedures used to assess exposure to diesel soot. Received: 30 December 1996 / Accepted: 21 February 1997