PDK1 ametronomic on the association between the UFT and CTX direct

Nt and a stable disease in patients with PDK1 other drug free up, we decided that our study on long-term use of oral tegafur in a fixed dose of 100 mg twice t design Possible base, about one-third of Ver Ffentlichung standard, the t Possible total dose. Justification of chemotherapy Astrong ametronomic on the association between the UFT and CTX direct result of their synergistic antitumor activity t in experimental mouse models of metastatic breast cancer and hepatocellular Ren carcinoma is based. The clinical combination of UFT and CTX has also been studied in women with metastatic breast cancer, but not a metronomic dosing of Ogawa et al. found that are daily treatment with UFT and CTX, both administered orally, rate.
Arelevant with a 35% response results of our study have been associated to the m use adjusted in future prospective clinical studies related, pharmacokinetics of UFT to the first entry of the drug to the effectiveness and predict PFS and OS of our patients. Tats Chlich showed the pharmacokinetic analysis of 27 patients after the first dose of UFT was a significant difference between the PD and SD groups on day 1 with 5-FU AUC and Cmax. The data by ROC analysis on the two parameters are obtained, suggest that patients with 5-FU and gr AUC 1313 as he h 9 lg / ml and 0.501 g / ml, a gr Ere clinical benefits have metronomic chemotherapy followed by a long Cmax PFS and OS accompanies. Although promising, further studies should be conducted to validate our initial findings. In fact, a perfect separation between PD and SD groups by ROC analysis is rare because of Zweig and Campbell says, because the distribution of the test results overlap. Despite the RESTRICTIONS LIMITATION this analysis, our results of the first test, a cut-off value in a clinically relevant pharmacokinetic Bev to be identified Lkerung. Interestingly, 5-FU concentrations were much lower than those obtained by the standard lists 5 FU chemotherapy in the first place directed against cells.Moreover tumor in patients heavily pre-treated, and whose tumors are the fluoropyrimidines, would recognize the levels expected no direct cytotoxic effect exercise.
In fact, it is plausible to suggest causes a different mechanism of metronomic UFT, perhaps more to the anti-angiogenic effect on proliferating endothelial cells and circulating endothelial precursor by a low concentration of 5-FU. The antiangiogenic effect of UFT are verst RKT, if non-toxic at low doses, kill given possible. Pr Clinical studies have shown that GHB and gamma-butyrolactone, the active metabolite of UFT, the expression of the struggle against the angiogenic activity are t part HA-1077 of the UFT. In particular, in vitro studies have shown that GHB inhibits endothelial cells with IC50 values of 25.8 ng / ml in our experimental setting, the mean plasma Cmax GHB may need during the treatment of 161-127 ng / ml varied. These concentrations are consistent with previous experience Ver Published, and especially with a direct anti-angiogenic activity t of GHB k Nnten synergy with low concentrations of 5-FU to create. The assumption that our metronomic UFT / CTX combination and timing of the CXB k Can also be an anti-angiogenic activity by a t was also marked.