Al's Comment:
Unfortunately, this trial didn't turn out well. They used cilengitide by itself and most children progressed quickly. This is an interesting drug. I think it will turn out that it is very useful - but in combination with other treatments as part of a comprehensive cocktail approach. I hope these negative results do not stop further research into combinations.
This also points out an important point when looking at results. They had a 3 year survivor who is still doing well. If that person happened to be in an online support group - the people in that group might tend to think - wow - this is a miracle drug - since they didn't see the other people in the trial doing poorly, they assume the trial worked. But what happens is that in some cases - particularly children, some people do well no matter what treatment you do to them. You need to compare the results of the experimental group to what would be expected with standard treatments and show an improvement. You can not judge by 1 or a few individual cases.
Posted on: 09/14/2013
Neuro Oncol. 2013 Sep 5. [Epub ahead of print]
Phase II study of cilengitide in the treatment of refractory or relapsed high-grade gliomas in children: A report from the Children's Oncology Group.
Macdonald TJ, Vezina G, Stewart CF, Turner D, Pierson CR, Chen L, Pollack IF, Gajjar A, Kieran MW.
Department of Pediatric Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, Georgia (T.J.M.); Department of Radiology, Children's National Medical Center, The George Washington University School of Medicine, Washington, DC (G.V.); Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee (C.F.S., D.T.); Department of Laboratory Medicine, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio (C.R.P.); Statistics, Children's Oncology Group Operations Center, Arcadia, California (L.C.); Department of Neurosurgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania (I.F.P.); Department of Neuro-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (A.G.); Department of Pediatric Hematology/Oncology, Dana-Farber Children's Hospital Cancer Center, Boston, Massachusetts (M.W.K.).
Abstract
BackgroundCilengitide, an αv integrin antagonist, has demonstrated activity in recurrent adult glioblastoma (GBM). The Children's Oncology Group ACNS0621 study thus evaluated whether cilengitide is active as a single agent in the treatment of children with refractory high-grade glioma (HGG). Secondary objectives were to investigate the pharmacokinetics and pharmacogenomics of cilengitide in this population.MethodsCilengitide (1800 mg/m2/dose intravenous) was administered twice weekly until evidence of disease progression or unacceptable toxicity. Thirty patients (age range, 1.1-20.3 years) were enrolled, of whom 24 were evaluable for the primary response end point.ResultsToxicity was infrequent and mild, with the exception of one episode of grade 2 pain possibly related to cilengitide. Two intratumoral hemorrhages were reported, but only one (grade 2) was deemed to be possibly related to cilengitide and was in the context of disease progression. One patient with GBM received cilengitide for 20 months and remains alive with continuous stable disease. There were no other responders, with median time to tumor progression of 28 days (range, 11-114 days). Twenty-one of the 24 evaluable patients died, with a median time from enrollment to death of 172 days (range, 28-325 days). The 3 patients alive at the time of this report had a follow-up time of 37, 223, and 1068 days, respectively.ConclusionsWe conclude that cilengitide is not effective as a single agent for refractory pediatric HGG. However, further study evaluating combination therapy with cilengitide is warranted before a role for cilengitide in the treatment of pediatric HGG can be excluded.
PMID: 24014381 [PubMed - as supplied by publisher]
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