Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

• DOI: 10.1007/s10456-012-9260-6
• Publication Date: 2012-03-01T15:03:30Z
• Authors: Giacomo Allegrini; Teresa Di Desidero; Maria Teresa Barl...; Anna Fioravanti; Paola Orlandi; Bastianina Canu; Silvio Chericoni; Fotios Loupakis; Antonello Di Paolo; Gianluca Masi; Andrea Fontana; Sara Lucchesi; Giada Arrighi; Mario Giusiani; Andrea Ciarlo; Giovanni Brandi; Romano Danesi; Robert S. Kerbel; Alfredo Falcone; Guido Bocci
• Keywords: Tegafur; Celecoxib; Pharmacodynamics; Refractory (planetary science); Bolus (digestion)

To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy plus celecoxib (CXB) for the treatment of patients with heavily pre-treated advanced gastrointestinal malignancies.Thirty-eight received 500 mg/mq(2) CTX i.v bolus on day 1 and, from 2, 50 mg/day p.o. 100 mg/twice a 200 CXB Tegafur, 5-FU, 5-FUH(2), GHB uracil pharmacokinetics were assessed. Plasma vascular endothelial growth factor (VEGF), soluble VE-cadherin (sVE-C) thrombospondin-1 (TSP-1) levels detected by ELISA real-time PCR CD133 gene expression peripheral blood mononuclear cell was also performed.Seventeen (45%) obtained stable disease (SD) median duration 5.8 ms (range, 4.2-7.4). Median progression free survival (PFS) overall (OS) 2.7 (95% CI, 1.6-3.9 ms) 7.1 4.3-9.9 ms), respectively. No toxicities grade >1 observed. Pharmacokinetics 27 (13/14, SD/progressive disease, PD) after first revealed that 5-FU AUC C(max) values greater than 1.313 h × μg/ml 0.501 μg/ml, respectively, statistically correlated stabilization prolonged PFS/OS. VEGF sVE-C plasma in PD group when compared to SD group. increased only patients.Metronomic well tolerated associated interesting activity. Potential predictive pharmacokinetic parameters pharmacodynamic biomarkers have been found.