Treatment of brain metastases from non-small cell lung cancer with whole-brain radiotherapy (wbrt) in combination with gefitinib (gft) or temozolomide (tmz): a randomized multicenter phase ii trial of the swiss group of clinical cancer research (sakk #70/03)

BACKGROUND: Patients with BM rarely survive .6 months and are commonly excluded from clinical trials. We aimed at improving outcome by exploring 2 combined modality regimens with at the time novel agents for which single-agent activity had been shown. METHODS: NSCLC patients with multiple BM were randomized to WBRT (10 × 3 Gy) and either GFT 250 mg p.o. daily or TMZ 75 mg/m2 p.o. daily ×21/28 days, starting on Day 1 of RT and to be continued until PD. Primary endpoint was overall survival, a Simon's optimal 2-stage design was based on assumptions for the 3-month survival rate. Cognitive functioning and quality of life were also evaluated. RESULTS: Fifty-nine patients (36 M, 23 F; 9 after prior chemo) were included. Median age was 61 years (range 46-82), WHO PS was 0 in 18 patients, 1 in 31 patients, and 2 in 10 patients. All but 1 patients had extracranial disease; 33 of 43 (TMZ) and 15 of 16 (GFT) had adenocarcinoma histology. GFT arm was closed early after stage 1 analysis when the prespecified 3-mo survival rate threshold (66%) was not reached, causes of death were not GFT related. Main causes of death were PD in the CNS 24%, systemic 41%, both 8%, and toxicity 10% [intestinal perforation (2 patients), pneumonia (2), pulmonary emboli (1), pneumonitis NOS (1), seizure (1)]. We summarize here other patients' characteristics for the 2 trial arms: TMZ (n ¼ 43)/GFT (n ¼ 16); median treatment duration: 1.6 /1.8 mo; Grade 3-4 toxicity: lymphopenia 5 patients (12%)/0; fatigue 8 patients (19%)/2 patients (13%). Survival data for TMZ/GFT arms: 3-month survival rate: 58.1% (95% CI 42.1-73)/62.5% (95% CI 35- 85); median OS: 4.9 months (95% CI 2.5-5.6)/6.3 months (95% CI 2.2- 14.6); median PFS: 1.8 months (95% CI 1.5-1.8)/1.8 (95% CI 1.1-3.9); median time to neurol. progr.: 8.0 months (95% CI 2.2-X)/4.8 (95% CI 3.9-10.5). In a model to predict survival time including the variables' age, PS, number of BM, global QL, total MMSE score, and subjective cognitive function, none of the variables accounted for a significant improvement in survival time. CONCLUSIONS: The combinations of WBRT with GFT or TMZ were feasible. However, in this unselected patient population, survival remains poor and a high rate of complication was observed. Four patients died as a result of high-dose corticosteroids. Preliminary evaluation of cognitive function andQL failed to show significant improvement. Indications and patient selection for palliative treatment should be revisited and careful monitoring and supportive care is required. Research and progress for this frequent clinical situation is urgently needed. Trial partly supported by AstraZeneca (Switzerland), Essex Chemie (Switzerland) and Swiss Federal Government.

In Vivo Profiling and Distribution of Known and Novel Phase I and Phase II Metabolites of Efavirenz in Plasma, Urine, and Cerebrospinal Fluid.

Efavirenz (EFV) is principally metabolized by CYP2B6 to 8-hydroxy-efavirenz (8OH-EFV) and to a lesser extent by CYP2A6 to 7-hydroxy-efavirenz (7OH-EFV). So far, most metabolite profile analyses have been restricted to 8OH-EFV, 7OH-EFV, and EFV-N-glucuronide, even though these metabolites represent a minor percentage of EFV metabolites present in vivo. We have performed a quantitative phase I and II metabolite profile analysis by tandem mass spectrometry of plasma, cerebrospinal fluid (CSF), and urine samples in 71 human immunodeficiency virus patients taking efavirenz, prior to and after enzymatic (glucuronidase and sulfatase) hydrolysis. We have shown that phase II metabolites constitute the major part of the known circulating efavirenz species in humans. The 8OH-EFV-glucuronide (gln) and 8OH-EFV-sulfate (identified for the first time) in humans were found to be 64- and 7-fold higher than the parent 8OH-EFV, respectively. In individuals (n = 67) genotyped for CYP2B6, 2A6, and CYP3A metabolic pathways, 8OH-EFV/EFV ratios in plasma were an index of CYP2B6 phenotypic activity (P < 0.0001), which was also reflected by phase II metabolites 8OH-EFV-glucuronide/EFV and 8OH-EFV-sulfate/EFV ratios. Neither EFV nor 8OH-EFV, nor any other considered metabolites in plasma were associated with an increased risk of central nervous system (CNS) toxicity. In CSF, 8OH-EFV levels were not influenced by CYP2B6 genotypes and did not predict CNS toxicity. The phase II metabolites 8OH-EFV-gln, 8OH-EFV-sulfate, and 7OH-EFV-gln were present in CSF at 2- to 9-fold higher concentrations than 8OH-EFV. The potential contribution of known and previously unreported EFV metabolites in CSF to the neuropsychological effects of efavirenz needs to be further examined in larger cohort studies.

The history of Lapland : containing a geographical description, and a natural history of that country; with an account of the inhabitants, their original, religion, customs, habits, marriages, conjurations, employments, &c. Written by John Scheffer, ... Translated from the last edition in Latin, and illustrated with many curious copper-cutts. To which are added, the travels of the King of Sweden's mathematicians into Lapland: the history of Livonia, and the wars there: also a journey into Lapland, Finland, &c. Written by Dr. Olof Rudbeck in the year 1701

Added engraved title page: The history of Lapland.

The expedition of Alexander the Great, first king of Persia : according to Quintus Curtius, Arrian, and others

Julkaisussa: Geographia classica : the geography of the ancients

Forced-air, vacuum, and hydro precooling of cauliflower (Brassica oleracea L. var. botrytis cv. Freemont): Part II. Determination of quality parameters during storage

Cauliflower heads, which were precooled using four different methods including vacuum, forced-air, and high and low flow hydro precooling, were stored under controlled atmosphere and room conditions. Controlled atmosphere conditions (CA) were as follows: 1°C temperature, 90 ± 5% relative humidity, and 0:21 [(%CO2:%O2) – (0:21) control] atmosphere composition. Room conditions (RC) were: 22±1°C temperature and 55-60% humidity. Various quality parameters of the cauliflower heads were assessed during storage (days 0, 7, 14, 21, 28, and 35) under controlled atmosphere and room conditions (days 0, 5, and 10). During storage, weight loss, deterioration rate, overall sensory quality score, hardness, and colour (L, a, b, C and α) were evaluated. In the present study, the strength and quality parameters of cauliflower under CA and RC conditions were obtained. Vacuum precooling was found to be most suitable method before cauliflower was submitted to cold storage and sent to market. Furthermore, the storage of cauliflower without precooling resulted in a significant decrease in quality parameters.

Francis Pélissier [champion de France de cross cyclo-pédestre le 7 mars 1920] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58363

Francis Pélissier [champion de France de cross cyclo-pédestre le 7 mars 1920] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58364

Francis Pélissier [champion de France de cross cyclo-pédestre le 7 mars 1920] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58365

Supplement to the late analysis of the public correspondence between our Cabinet and those of France and G. Britain /

Caption title.

The History of the Consulate & The Empire of France Under Napoleon

The book is stamped in the front and back with the "Upper Canada College" crest. There is also a plate within the book indicating that it was presented to H.K. Woodruff by the senate as an acknowledgement of merit and as a reward for general proficiency in Upper Canada College in June, 1878. On the top of this plate it says: 1st Form Prize, Upper Modern Form. The full text is available in the Brock University Special Collections and Archives or view the full text at the following link: http://www.archive.org/details/consulateempire1and2thie