PK-PD modeling of individual lesion FDG-PET response to predict overall survival in patients with sunitinib-treated gastrointestinal stromal tumor.
Pharmacometric models were developed to characterize the relationships between lesion-level tumor metabolic activity, as assessed by the maximum standardized uptake value (SUVmax) obtained on [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), tumor size, and overall survival (OS) in 66 patients with gastrointestinal stromal tumor (GIST) treated with intermittent sunitinib. An indirect response model in which sunitinib stimulates tumor loss best described the typically rapid decrease in SUVmax during on-treatment periods and the recovery during off-treatment periods. Substantial interindividual and interlesion variability were identified in SUVmax baseline and drug sensitivity. A parametric time-to-event model identified the relative change in SUVmax at one week for the lesion with the most pronounced response as a better predictor of OS than tumor size. Based on the proposed modeling framework, early changes in FDG-PET response may serve as predictor for long-term outcome in sunitinib-treated GIST.
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
E
E
Schindler
Pfizer Inc., La Jolla, California, USA.
M A
MA
Amantea
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
M O
MO
Karlsson
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
L E
LE
Friberg
D000328:Adult; D019788:Fluorodeoxyglucose F18; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008954:Models, Biological; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D049268:Positron-Emission Tomography / Q000379:methods; D011758:Pyrroles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D000077210:Sunitinib; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D047368:Tumor Burden
D007211:Indoles; D011758:Pyrroles; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000077210:Sunitinib