© 2003 by Society
© 2003 by the Society forNeuro-Oncology
A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 incombination with carboplatin administered intravenously for the treatment ofrecurrent malignant glioma
Department of Neurological Surgery, University ofCalifornia San Francisco, San Francisco, CA 94143 (M.D.P); Department of Neurology, University of Texas, SouthwesternMedical Center, Dallas, TX 75390 (S.C.S.); Departmentof Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115(H.A.F.); Department of Neurology, University ofTexas, M.D. Anderson Cancer Center; Houston, TX 77030 (K.J.); Department of Neurology, Massachusetts General Hospital,Boston, MA 02214 (F.H.); Department of Neurology,State University of New York at Buffalo, Buffalo, NY 14209 (L.M.); Department of Neurology, Columbia Presbyterian MedicalCenter, New York, NY 10032 (M.R.F.); Moffitt CancerCenter & Research Institute, Tampa, FL 33612 (S.P.), Division of Hematology/Oncology, University of Miami Schoolof Medicine, Miami, FL 33136 (L.F.); Departments ofMedical Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA52242 (T.J.J.); Alkermes, Inc., Cambridge, MA 02139(K.F., W.G.); USA
2 Address correspondence and reprint requests to Michael Prados, M.D.,University of California San Francisco, 400 Parnassus Avenue, Room A808, SanFrancisco, CA 94143-0372(PradosM{at}neurosurg.ucsf.edu).
 |
Abstract |
|---|
RMP-7, a bradykinin analog, temporarily increases the permeability of theblood-brain tumor barrier to chemotherapy drugs like carboplatin. We conducteda randomized, controlled trial of carboplatin and RMP-7 versus carboplatin andplacebo in patients with recurrent malignant glioma. The primary outcomemeasure was time to tumor progression (TTP). Adults with recurrentglioblastoma multiforme or anaplastic glioma were randomized in a 1:1 ratio toreceive carboplatin and either RMP-7 or placebo. Radiation therapy had failedin all patients, and they may have received prior chemotherapy. Carboplatin(dosed to achieve an area under the curve of 5 mg/ml x time for patients whohad received prior chemotherapy, or 7 mg/ml x time for those who had not) wasgiven intravenously every 4 weeks, followed by intravenous infusion of eitherRMP-7 or placebo (300 ng/kg). TTP, tumor response, neuropsychologicalassessments, functional independence, and quality of life assessments wereanalyzed every 4 weeks. There were 122 patients enrolled, 62 in the RMP-7 andcarboplatin group and 60 in the placebo and carboplatin group. Median TTP was9.7 weeks (95% CI, 8.3-12.6 weeks) for the RMP-7 and carboplatin group and 8.0weeks (95% CI, 7.4-12.6 weeks) for the placebo and carboplatin group. Mediansurvival times were 26.9 weeks (95% CI, 21.3-37.6 weeks) for the RMP-7 groupand 19.9 weeks (95% CI, 15.0-31.3 weeks) for the placebo group. No differenceswere noted for time to worsening of neuropsychological assessments, functionalindependence, or quality of life assessments. The use of RMP-7 had no effecton the pharmacokinetics or toxicity of carboplatin. At the dose and scheduleused in this trial, RMP-7 did not improve the efficacy of carboplatin. Recentpreclinical pharmacokinetic modeling of RMP-7 suggests that higher doses ofRMP-7 may be required to increase carboplatin delivery to tumor.
Received September 5, 2002; Accepted November 11, 2002
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. F. Deeken and W. Loscher The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses Clin. Cancer Res., March 15, 2007; 13(6): 1663 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Bodell, A. P. Bodell, and D. D. Giannini Levels and distribution of BCNU in GBM tumors following intratumoral injection of DTI-015 (BCNU-ethanol) Neuro Oncology, January 1, 2007; 9(1): 12 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Akabani, D. A. Reardon, R. E. Coleman, T. Z. Wong, S. D. Metzler, J. E. Bowsher, D. P. Barboriak, J. M. Provenzale, K. L. Greer, D. DeLong, et al. Dosimetry and Radiographic Analysis of 131I-Labeled Anti-Tenascin 81C6 Murine Monoclonal Antibody in Newly Diagnosed Patients with Malignant Gliomas: A Phase II Study J. Nucl. Med., June 1, 2005; 46(6): 1042 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Grossman, J. B. Alavi, J. G. Supko, K. A. Carson, R. Priet, F. A. Dorr, J. S. Grundy, and J. T. Holmlund Efficacy and toxicity of the antisense oligonucleotide aprinocarsendirected against protein kinase C-{alpha} delivered as a 21-day continuousintravenous infusion in patients with recurrent high-grade astrocytomas Neuro Oncology, January 1, 2005; 7(1): 32 - 40. [Abstract] [PDF]
|
|
|
|
 |
|
 S. R. Burzynski Letter to the Editor Integr Cancer Ther, September 1, 2004; 3(3): 200 - 200. [PDF]
|
|
|
|
|
|
S. R. Burzynski, R. I. Lewy, R. Weaver, T. Janicki, G. Jurida, M. Khan, C. B. Larisma, J. Paszkowiak, and B. Szymkowski Long-Term Survival and Complete Response of a Patient with Recurrent Diffuse Intrinsic Brain Stem Glioblastoma Multiforme Integr Cancer Ther, September 1, 2004; 3(3): 257 - 261. [Abstract] [PDF]
|
|
|
|
|
|
S. R. Burzynski The Present State of Antineoplaston Research (1) Integr Cancer Ther, March 1, 2004; 3(1): 47 - 58. [Abstract] [PDF]
|
|