Aims. To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy plus celecoxib (CXB) for the treatment of patients with heavily pre-treated advanced gastrointestinal malignancies. Methods. Thirty-eight patients received 500 mg/mq2 CTX i.v bolus on day 1 and, from day 2, 50 mg/day CTX p.o. plus 100 mg/twice a day UFT p.o. and 200 mg/twice a day CXB p.o. Tegafur, 5-FU, 5-FUH2, GHB and uracil pharmacokinetics were assessed. Plasma vascular endothelial growth factor (VEGF), soluble VE-cadherin (sVE-C) and thrombospondin-1 (TSP-1) levels were detected by ELISA and real-time PCR of CD133 gene expression on peripheral blood mononuclear cell was also performed. Results Seventeen patients (45%) obtained stable disease (SD) with a median duration of 5.8 ms (range, 4.2–7.4). Median progression free survival (PFS) and overall survival (OS) were 2.7 ms (95% CI, 1.6–3.9 ms) and 7.1 ms (95% CI, 4.3–9.9 ms), respectively. No toxicities of grade >1 were observed. Pharmacokinetics of 27 patients (13/14, SD/progressive disease, PD) after the first treatment of UFT revealed that 5-FU AUC and Cmax values greater than 1.313 h x microg/ml and 0.501 microg/ml, respectively, were statistically correlated with stabilization of disease and prolonged PFS/OS. VEGF and sVE-C plasma levels were greater in the PD group when compared to SD group. CD133 expression increased only in the PD patients. Conclusion. Metronomic UFT and CTX with CXB in heavily pre-treated gastrointestinal patients were well tolerated and associated with interesting activity. Potential predictive pharmacokinetic parameters and pharmacodynamic biomarkers have been found.
|Autori:||Allegrini, G; Di Desidero, T; Barletta, Mt; Fioravanti, A; Orlandi, P; Canu, B; Chericoni, S; Loupakis, F; DI PAOLO, Antonello; Masi, G; Fontana, A; Lucchesi, S; Arrighi, G; Giusiani, Mario; Ciarlo, A; Brandi, G; Danesi, Romano; Kerbel, Rs; Falcone, Alfredo; Bocci, Guido|
|Titolo:||Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers|
|Anno del prodotto:||2012|
|Digital Object Identifier (DOI):||10.1007/s10456-012-9260-6|
|Appare nelle tipologie:||1.1 Articolo in rivista|