A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer

BACKGROUND: Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. METHODS: A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m(2 )twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m(2 )for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. RESULTS: Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. CONCLUSION: There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent

Quarto ventrículo isolado: relato de dois casos Isolated fourth ventricle: report of two cases

São descritos dois casos de quarto ventrículo isolado sendo o primeiro decorrente de hemorragia cerebelar e o segundo de hidrocefalia congênita com múltiplas revisões de válvula e cisto de Dandy-Walker. O tratamento cirúrgico é revisado na literatura. A abordagem direta à fossa posterior acha-se indicada nos casos de cisto no interior do quarto ventrículo. Naqueles sem a presença de cisto, deve-se empregar sistema de drenagem do quarto ventrículo, independente da drenagem supratentorial.<br>Two cases of isolated fourth ventricle are reported, the first due to cerebellar haemorrhage, and the second due to congenital hydrocephalus with multiple shunt revisions and Dandy-Walker cyst. In our opinion, there are two basic treatment for isolated forth ventricle. The direct approach to the fourth ventricle is indicated when there is presence of an intraventricular cyst. The fourth ventricular shunting, independent of the supratentorial shunt, is the best treatments for patients with an isolated fourth ventricle without the presence of a cyst

Incongruence between test statistics and <it>P </it>values in medical papers

<p>Abstract</p> <p>Background</p> <p>Given an observed test statistic and its degrees of freedom, one may compute the observed <it>P </it>value with most statistical packages. It is unknown to what extent test statistics and <it>P </it>values are congruent in published medical papers.</p> <p>Methods</p> <p>We checked the congruence of statistical results reported in all the papers of volumes 409–412 of <it>Nature </it>(2001) and a random sample of 63 results from volumes 322–323 of <it>BMJ </it>(2001). We also tested whether the frequencies of the last digit of a sample of 610 test statistics deviated from a uniform distribution (i.e., equally probable digits).</p> <p>Results</p> <p>11.6% (21 of 181) and 11.1% (7 of 63) of the statistical results published in <it>Nature </it>and <it>BMJ </it>respectively during 2001 were incongruent, probably mostly due to rounding, transcription, or type-setting errors. At least one such error appeared in 38% and 25% of the papers of <it>Nature </it>and <it>BMJ</it>, respectively. In 12% of the cases, the significance level might change one or more orders of magnitude. The frequencies of the last digit of statistics deviated from the uniform distribution and suggested digit preference in rounding and reporting.</p> <p>Conclusions</p> <p>This incongruence of test statistics and <it>P </it>values is another example that statistical practice is generally poor, even in the most renowned scientific journals, and that quality of papers should be more controlled and valued.</p