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Abstract
Highlights
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- Mathematical modeling of CA-125 kinetics in ROC patients enables understanding of the CA-125 time-change components: cancer production, chemotherapy effect, elimination.
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- The contradictory surrogacy of GCIG-defined CA-125 response regarding progression free survival reported by Lee et al (JNCI 2011;103:1338) was confirmed.
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- The modeled CA-125 elimination rate KELIM, potentially assessable in routine, may have promising predictive value regarding progression free survival.
Background
Unexpected
results were recently reported about the poor surrogacy of Gynecologic
Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian
cancer (ROC) patients. Mathematical modeling may help describe CA-125
decline dynamically and discriminate prognostic kinetic parameters (technical info).
Methods
Data
from CALYPSO phase III trial comparing 2 carboplatin-based regimens in
ROC patients were analyzed. Based on population kinetic approach, serum
[CA-125] concentration-time profiles during first 50 treatment days were
fit to a semi-mechanistic model with following parameters:
“d[CA-125]/dt = (KPROD * exp (BETA*t)) * Effect –KELIM*[CA-125]” with
time, t; tumor growth rate, BETA; CA-125 tumor production rate, KPROD;
CA-125 elimination rate, KELIM and K-dependent treatment indirect
Effect. The predictive values of kinetic parameters were tested
regarding progression-free survival (PFS) against other reported
prognostic factors.
Results
Individual
CA-125 kinetic profiles from 895 patients were modeled. Three kinetic
parameters categorized by medians had predictive values using univariate
analyses: K; KPROD and KELIM (all P<0.001). Using Cox multivariate
analysis, 5 independent predictors of PFS remained significant: GCIG
CA-125 response (favoring carboplatin-paclitaxel arm), treatment arm,
platinum free-interval, measurable lesions and KELIM (HR = 0.53; 95% CI
0.45-0.61; P<0.001).
Conclusions
Mathematical
modeling of CA-125 kinetics in ROC patients enables understanding of
the time-change components during chemotherapy. The contradictory
surrogacy of GCIG-defined CA-125 response was confirmed. The modeled
CA-125 elimination rate KELIM, potentially assessable in routine, may
have promising predictive value regarding PFS. Further validation of
this predictive marker is warranted.
There are no figures or tables for this document.
- ☆
- Presentation during congress: This study was presented during 2011 ASCO Annual Meeting (Abstract 5065).
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