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randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in
combination with carboplatin administered intravenously for the treatment of
recurrent malignant glioma
Prados MD, Schold SC JR SC, Fine HA, Jaeckle K, Hochberg F, Mechtler L,
Fetell MR, Phuphanich S, Feun L, Janus TJ, Ford K, Graney W
Department of Neurological Surgery, University of California San
Francisco, 94143, USA.
PradosM@neurosurg.ucsf.edu
RMP-7, a bradykinin analog, temporarily increases the permeability of the
blood-brain tumor barrier to chemotherapy drugs like carboplatin.
We conducted a randomized, controlled trial of carboplatin and RMP-7 versus
carboplatin and placebo in patients with recurrent malignant glioma.
The primary outcome measure was time to tumor progression (TTP).
Adults with recurrent glioblastoma multiforme or anaplastic glioma were
randomized in a 1:1 ratio to receive carboplatin and either RMP-7 or
placebo.
Radiation therapy had failed in 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 who had received prior chemotherapy, or 7 mg/ml x time for those who
had not) was given intravenously every 4 weeks, followed by intravenous infusion
of either RMP-7 or placebo (300 ng/kg).
TTP, tumor response, neuropsychological assessments, functional independence,
and quality of life assessments were analyzed every 4 weeks.
There were 122 patients enrolled, 62 in the RMP-7 and carboplatin group and 60
in the placebo and carboplatin group.
Median TTP was 9.7 weeks (95% CI, 8.3-12.6 weeks) for the RMP-7 and carboplatin
group and 8.0 weeks (95% CI, 7.4-12.6 weeks) for the placebo and carboplatin
group.
Median survival times were 26.9 weeks (95% CI, 21.3-37.6 weeks) for the RMP-7
group and 19.9 weeks (95% CI, 15.0-31.3 weeks) for the placebo group.
No differences were noted for time to worsening of neuropsychological
assessments, functional independence, or quality of life assessments.
The use of RMP-7 had no effect on the pharmacokinetics or toxicity of
carboplatin.
At the dose and schedule used in this trial, RMP-7 did not improve the efficacy
of carboplatin.
Recent preclinical pharmacokinetic modeling of RMP-7 suggests that higher doses
of RMP-7 may be required to increase carboplatin delivery to tumor.
PMID:
12672281 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12672281&dopt=Abstract |
