Tumor Growth Rate (TGR) is an early indicator of anti-tumor drug activity in phase I clinical trials
A partir de données médicales portant sur 253 patients ayant été inclus dans 20 essais de phase I, cette étude française analyse l'intérêt du critère de "taux de croissance tumorale" pour évaluer l'activité antitumorale d'un traitement expérimental
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) indpendent association with PFS; and (iii) It reveals drug-specific profiles; suggesting potential utility for guiding the further development of the investigational drugs.
Clinical Cancer Research , article en libre accès, 2013