FCR to 5-deoxy-5-fluorouridine (5-DFUR). The third and last step occurs at the tumor site by the tumor-associated angiogenic factor thymidine phosphorylase (TP), metabolizing 5-DFUR to 5- FU. Therefore, 5-FU is preferentially generated in tumor tissue when Monensin sodium salt compared with normal body tissue.The cytotoxic action of 5-FU is mostly based on the inhibition of thymidylate synthase (TS). This effect is mediated by the 5-FU metabolite 5-fluoro-2-deoxyuridine-5emonophosphate (FdUMP), which blocks the de novo synthesis of thymidylate (dTMP) by forming a ternary complex with TS and the essential co-factor 5,10- methylenetetrahydrofolate (CH2-THF) leading to a defective DNA synthesis.
Whenever the formation of cell DNA from thymidylate is slowed down, the prolonged cell cycle allows excess synthesis of RNA and other cytoplasmic components including Kinetin hemoglobin, leading to the increased size of red blood cells in megaloblastic anemia. This can be the result of severe deficiencies of vitamin B12 and folic acid, as well as capecitabine treatment as a result of the inhibition of TS in erythroid precursor cells. The consistent finding of macrocytosis during capecitabine treatment, both when given at standard doses and at metronomic doses, may suggest that there is good pharmacodynamic evidence of adequate capecitabine dosage even when it is given at daily low dose.Bevacizumab is a humanized monoclonal antibody directed against VEGF. There are no data on the possible role of bevacizumab on the development of macrocytosis.
In patients with metastatic renal cell carcinoma, however, macrocytosis was a common purchase Phlorizin occurrence after treatment with sunitinib but not sorafenib, two small molecules that inhibit the vascular endothelial growth factor and related receptors. Macrocytosis was also noted in 42% of gastrointestinal stromal tumors (GIST) patients receiving imatinib, a small molecule that has antitumor effect through inhibition of c- KIT, which is constitutively activated in GIST. Imatinib and sunitinib may lead to macrocytosis through c-KIT inhibition, although the precise mechanisms of c-kitemediated macrocytosis require further investigation. Sorafenib has much weaker inhibitory activity against c-kit, therefore this could explain why macrocytosis was not observed with sorafenib treatment. In our analysis, the onset of macrocytosis inversely related to risk of disease progression (Hazard Ratio: 0.45; 95% CI: 0.22e0.92, p-value 0.028) in 69 patients treated with metronomic capecitabine plus cyclophosphamide and i.v. bevacizumab for muscular metastatic breast cancer.
In the paper byWenzel et a higher MCV values were seen in patients with tumor remission or stable disease rather than in patients with tumor progression, but the difference was not statistically significant. This might be due first of all to the different tumor types and order Oridonin various treatment schedules considered in the paper, as compared to our homogeneous cohort of metastatic breast cancer patients. Secondly, the capecitabine schedule considered in the paperwas the standard one (2500 mg/m2/day for 14 days every 21 days) while in our report it was a metronomic one (1500 mg/day continuously).