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From: Subject: SpringerLink - Article Date: Thu, 25 May 2006 08:46:34 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C67FD7.BA31A630" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C67FD7.BA31A630 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://springerlink.metapress.com/(vx24pl55qrpm0355cnboxi45)/app/home/contribution.asp?referrer=parent&backto=issue,7,16;journal,2,331;linkingpublicationresults,1:100508,1 =EF=BB=BF SpringerLink - Article

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Cancer Chemotherapy and = Pharmacology=20 Publisher: Springer=20 Berlin / Heidelberg ISSN: 0344-5704=20 (Paper) 1432-0843 (Online) DOI: 10.1007/s00280-005-0172-7=20 Issue: =20 Volume 58, Number 3
Date: =20 September 2006 Pages: 343=20 - 347

Original Article

Phase II = trial of=20 intravenous lobradimil and carboplatin in childhood = brain=20 tumors: a report from the Children=E2=80=99s Oncology = Group

K. Warren¹, = R. Jakacki³,=20 B. Widemann², = A. Aikin²,=20 M. Libucha², = R. Packer⁴,=20 G. Vezina⁴, = G. Reaman⁵,=20 D. Shaw⁵, M. Krailo⁵,=20 C. Osborne⁶, = J. Cehelsky⁶,=20 D. Caldwell⁶, = J. Stanwood⁶,=20 S. M. Steinberg⁷ and=20 F. M. Balis²

(1) National Cancer=20 Institute/Neuro-Oncology Branch , Bldg 82, Rm = 219, 9030=20 Old Georgetown Road, Bethesda, = MD 20892-8200,=20 USA

(2) Pediatric Oncology = Branch,=20 National Cancer Institute, Washington, DC,=20 USA

(3) Children=E2=80=99s = Hospital of=20 Pittsburgh, Washington, DC,=20 USA

(4) Children=E2=80=99s = National Medical=20 Center, Washington, DC, = USA

(5) Children=E2=80=99s = Oncology Group ,=20 Cambridge, MA, = USA

(6) Alkermes, Inc, = Cambridge,=20 MA, USA

(7) Biostatistics and = Data=20 Management Section, National Cancer Institute,=20 Washington, DC, = USA

Received:=20 = 23 August 2005  Accepted:=20 = 12 December 2005  Published=20 online: 12 January 2006

Abstract  =20 Backround: Lobradimil is a synthetic bradykinin = analog=20 that rapidly and transiently increases the = permeability of the=20 blood-brain barrier (BBB). The combination of = lobradimil and=20 carboplatin was studied in pediatric patients with = primary=20 brain tumors in a phase II trial, the primary = endpoints of=20 which were to estimate the response rate and time to = disease=20 progression. Patients and methods: Patients = were=20 stratified by histology into five cohorts: brainstem = glioma,=20 high-grade glioma, low-grade glioma, = medullobastoma/primitive=20 neuroectodermal tumor (PNET), and ependymoma. Patients = received carboplatin adaptively dosed to achieve a = target AUC=20 of 3.5 mg min/ml per day = (7 mg=C2=B7min/ml/cycle)=20 intravenously over 15 min on 2 consecutive days = and=20 lobradimil 600 ng/kg ideal body weight/day on 2=20 consecutive days each 28 day cycle. = Results:=20 Forty-one patients, age 2=E2=80=9319 years, were = enrolled; 38=20 patients, including 1 patient ultimately determined to = have=20 atypical neurocytoma, were evaluable for response. No=20 objective responses were observed in the brainstem = glioma=20 (n=3D12) and high-grade glioma (n=3D9) = cohorts,=20 although two patients with high-grade glioma had = prolonged=20 disease stabilization (>6 months). The study = was=20 closed for commercial reasons prior to achieving the = accrual=20 goals for the ependymoma (n=3D8), = medulloblastoma/PNET=20 (n=3D6) and low-grade glioma (n=3D2) = cohorts,=20 although responses were observed in 1 patient with = PNET and 2=20 patients with ependymoma. Conclusion: The = combination=20 of lobradimil and carboplatin was inactive in = childhood=20 high-grade gliomas and brainstem gliomas.

Keywords  Brain=20 = tumors - Lobradimil - Children - Ependymoma= - Glioma - Medulloblastoma - Phase=20 II - RMP-7

=

3D"Contact K. Warren
= Email:=20 warrenk@mail.nih.gov
= Phone:=20 +1-301-4026298
Fax:=20 = +1-301-4802246

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underline } A.bodycolor3 { COLOR: #003399; TEXT-DECORATION: none } A.bodycolor3:active { COLOR: #003399; TEXT-DECORATION: none } A.bodycolor3:hover { COLOR: #ff6600; TEXT-DECORATION: underline } A.bodycolor3high { COLOR: #ff6600; TEXT-DECORATION: underline } ------=_NextPart_000_0000_01C67FD7.BA31A630--