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abstract
Purpose: RECIST evaluation does not take
into account the pre-treatment tumor kinetics and may provide incomplete
information
regarding experimental drug activity. Tumor Growth Rate (TGR) allows for a dynamic and quantitative assessment of the tumor
kinetics. How TGR varies along the introduction of
experimental therapeutics and is associated with outcome in phase I
patients
remains unknown.
Experimental designs: Medical records from all
patients (n=253) prospectively treated in 20 phase I trials were
analyzed.
TGR was computed during the pre-treatment period
(REFERENCE) and the EXPERIMENTAL period. Associations between TGR,
standard
prognostic scores (RMH score) and outcome (PFS, OS)
were computed (multivariate analysis).
Results: We observed a reduction of TGR between the
REFERENCE vs. EXPERIMENTAL periods (38% vs. 4.4%, P<.00001).
Although
most patients were classified as stable disease
(65%) or progressive disease (25%) by RECIST at the first evaluation,
82%
and 65% of them exhibited a decrease in TGR,
respectively. In a multivariate analyses, only the decrease of TGR was
associated
with PFS (P=.004), whereas the RMH score was the
only variable associated with OS (P=.0008). Only the investigated
regimens
delivered were associated with a decrease of TGR
(P<.00001, multivariate analysis). Computing TGR profiles across
different
clinical trials reveals specific patterns of
antitumor activity.
Conclusions: Exploring TGR in phase I patients is
simple and provides clinically relevant information: (i) an early and
subtle
assessment of signs of antitumor activity; (ii)
independent association with PFS; and (iii) It reveals drug-specific
profiles;
suggesting potential utility for guiding the
further development of the investigational drugs.
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