Xeloda© for metastatic breast cancer – a highly effective oral agent
Oral Xeloda© – effective anti-tumour activity in colorectal cancer
Xeloda© is a highly active oral fluoropyrimidine designed to generate the active drug 5-fluorouracil (5-FU) preferentially in tumour tissue.
Xeloda© is rapidly and extensively absorbed through the gut as an intact molecule and is then metabolized to 5-FU in three steps.1,2
Enzymatic conversion of Xeloda© to 5-FU. From Leonard 2001,2 with permission.
The enzyme thymidine phosphorylase, which is implicated in the final conversion step, is significantly more active in tumour tissue than in adjacent healthy tissue.3,4 Thus, the final pathway in the metabolism of Xeloda© to 5-FU takes place predominantly in tumour cells, concentrating the active component at the desired site of action and minimizing systemic exposure to 5-FU.Animal models have shown that, following administration of Xeloda© , the concentration of 5-FU is significantly (127-fold) higher within tumour tissue than in the plasma.5
Xeloda© , administered daily for 2 weeks followed by 1 week of rest, mimics continuous infusion of 5-FU without the inconvenience, cost and complications associated with hospital-based i.v. infusions.
REFERENCES
1 Miwa M, Ura M, Nishida M et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998; 34: 1274–81.
2 Leonard RC. Oral fluoropyrimidines among the new drugs for patients with metastatic breast cancer. Br J Cancer 2001; 84: 1437–42. 3 Kono A, Hara Y, Sugata S et al. Activation of 5'-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors. Chem Pharm Bull (Tokyo) 1983; 31: 175–8.
4 Shimma N, Umeda I, Arasaki M et al. The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine. Bioorg Med Chem 2000; 8: 1697–706.
5 Ishikawa T, Utoh M, Sawada N et al. Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem Pharmacol 1998; 55: 1091–7. |