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A prospective blinded study of the predictive
value of an extreme drug resistance assay in patients receiving CPT-11 for
recurrent glioma
Parker RJ, Fruehauf JP, Mehta R, Filka E, Cloughesy T
Oncotech, Inc., Tustin, CA 92780, USA.
This adjunct to a prospective phase II blinded study of 48 patients with
recurrent malignant glioma evaluated the predictive reliability of an extreme
drug resistance (EDR) to identify clinical resistance to irinotecan (CPT-11),
using fresh tumor biopsies obtained from recurrent patients immediately prior to
their first dose of CPT-11 therapy.
In vitro tumor response to SN38 (bioactive species of CPT-11 used in the EDR
assay) determined prior to treatment was correlated with objective response,
time to tumor progression (TTP) and survival following the administration of
CPT-11.
SN38 activity was tested in 19 of 29 tumors, with 15 of 18 assay results
evaluable for correlation with clinical outcomes.
In vitro drug resistance was classified as either extreme, intermediate (IDR),
or low (LDR).
TTP and survival were estimated by the Kaplan-Meier method, and compared using
the Mantel-Haenszel log-rank and Fisher's exact test statistics.
In vitro tumor response was bifurcated into either EDR (n = 4) or IDR/LDR (n =
11) categories for comparison with outcomes.
Results correlated significantly with both TTP and survival. Median TTP for
IDR/LDR cases was 3 months versus 6 weeks for EDR cases (log-rank test; p =
0.0288, hazards ratio = 3.06).
A 13-week median survival for EDR cases was significantly shorter compared to 38
weeks for IDR/LDR cases (p = 0.029).
Further, 100-day survival favored the IDR/LDR cases (Fisher's exact test; p =
0.008).
At last follow-up, two of three survivors were patients who had tumors IDR/LDR
to SN38.
These prospective data support the notion that patients should avoid agents to
which their tumor demonstrates EDR.
PMID: 15015670 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15015670
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