title: Feasibility of CT scan-guided Tru-Cut serial liver biopsies to evaluate pharmacodynamic endpoints in patients with liver metastasis treated with experimental drugs.
abstract: We assessed the feasibility of using computed tomographically guided, Tru-Cut serial liver biopsies to perform pharmacodynamic studies in patients with liver metastasis who had been treated with experimental drugs. Twenty-three patients with liver metastasis were enrolled in two protocols for evaluation of the response to two new biologic drugs: a farnesyltransferase inhibitor and a tyrosine kinase inhibitor of the epidermal growth factor receptor. Computed tomographically guided Tru-Cut biopsies with an 18-gauge needle were performed. The procedure was performed at baseline and 2, 6, and 24 h after starting the administration of the drug. The procedures were scheduled on an outpatient basis. We obtained 271 samples (168 from metastatic lesions and 103 from surrounding normal liver tissue) from 23 patients. Biochemical determination of farnesyltransferase activity and different immunohistochemistry stainings (pEGRF, pMAPK, p27, Ki67, and apoptosis) of the signal transduction pathway were determined in each tissue sample, and all scheduled tissue assays were performed with the tissues obtained. Complete serial biopsies were performed in 20 patients. Three patients were excluded due to minor complications after the first biopsy. The morbidity rate in relation to the number of procedures was 1.1% (three of 271 samples). We found serial liver biopsies using Tru-Cut to be a safe and easy procedure. In our series, we could evaluate samples for molecular changes that influence the optimal dose, sequence, and schedule of the new antineoplastic agents.
authors.affiliation: Radiology Department, Vall d'Hebron University Hospital, Barcelona, Spain. JHildalgoP@santpau.es
authors.forename: A
authors.initials: A
authors.lastname: Hidalgo
authors.forename: J
authors.initials: J
authors.lastname: Tabernero
authors.forename: F
authors.initials: F
authors.lastname: Rojo
authors.forename: I
authors.initials: I
authors.lastname: Marimon
authors.forename: J
authors.initials: J
authors.lastname: Andreu
authors.forename: J
authors.initials: J
authors.lastname: Baselga
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D001707:Biopsy, Needle / Q000295:instrumentation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D051231:Farnesyltranstransferase; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases