Capecitabine efficacy

Capecitabine is an oral prodrug of 5-FU that also is effective in the adjuvant setting and is being evaluated as a replacement for 5-FU for patient convenience and safety reasons. Data suggest that capecitabine is at least equivalent to 5-FU and leucovorin in efficacy and is better tolerated by patients.24 Consequently, most practitioners feel that capecitabine is an acceptable alternative to IV 5-FU plus leucovorin. However, the role of capecitabine with additional chemotherapy agents such as oxaliplatin requires further study... 

Capecitabine, an oral prodrug of 5-FU, has efficacy and safety profiles similar to those of IV infusion of 5-FU. 

The recent availability of oral formulations of 5-FU, may provide not only an improvement in the ease of administration and the efficacy of fluoropyrimidine therapy, but also alleviate complications related to the catheters. Such agents include uracil tegafur (UFT) and capecitabine (Xeloda). 

Sawada N, IshikawaT, Sekiguchi F, Tanaka Y, IshitsukaH. X-ray irradiation induces thymidine phos-phorylase and enhances the efficacy of capecitabine in human xenografts. Clin Cancer Res 1999 5(10) 2948-2953. 

Ishikawa T, Sekiguchi F, Fukase Y et al. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res 1998 58 685-690. 

In parallel to these studies, carbamate compounds 1 and 11-14 were assessed for their antitumor efficacy in mouse cancer xenograft models.15 When implanted human colon cancer CXF280 xenografts were grown within mice for fourteen days, doses of test compounds were administered orally. After a three-week regimen, excised tumor volumes were measured and the percent inhibition of tumor growth was calculated. From this investigation, capecitabine (1) was found to be the most effective treatment, and was furthermore found not to cause intestinal toxicity.16 All of these preclinical observations contributed to the selection of capecitabine as a candidate for further development. 

Two Phase III clinical studies of orally administered capecitabine in over 1,200 patients with untreated metastatic colorectal cancer demonstrated at least equal efficacy and improved tolerability versus the Mayo Clinic regimen of intravenous 5-fluorouracil/leucovorin administration. The overall response rate for patients taking capecitabine orally was 21%, versus 14% for the intravenous 5-FU/leucovorin regimen. A median 53-month follow-up revealed a three-year disease-free survival rate of 66% for capecitabine versus 63% for 5-FU/leucovorin patients. International Phase II trials also demonstrated therapeutic benefits of capecitabine monotherapy for women with metastatic breast cancer that was either resistant to both paclitaxel and anthracycline therapy. Orally administered at the twice-daily 1,250 mg/m2 regimen (cycles of two weeks of therapy followed by a week of rest), the tumor response rate was in the range of 20-25%. In addition, combination of capecitabine with a taxane yielded a unique survival benefit compared to the previous standard of taxane monotherapy for anthracycline-resistant breast cancer.13,14... 

CAPECITABINE ANTIGOUT DRUGS-ALLOPURINOL Possible 1 efficacy of capecitabine Capecitabine is a prodrug for fluorouracil it is uncertain at which point allopurinol acts on the metabolic pathway Manufacturers recommend avoiding co-administration... 

In addition to 5-FU, its fluorinated prodrugs such as gemzar, floxuridine, capecitabine, tegafur uracil, etc. have also been evaluated using 19F MR spectroscopy, at least in the laboratory or in animal models [3, 7-10], Improved efficacy of 5-FU has been achieved by using it in combination with other medications that either modulate its uptake or/and increase its metabolism. 19F MR has been used to measure the modulation of 5-FU... 

Wagstaff AJ, Ibbotson T, Goa KL. Capecitabine areview of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drags 2003 63 217-236. 

Capecitabine is an acceptable alternative to intravenous fluorouracil for metastatic colorectal cancer, as it provides similar efficacy and its oral dosing may offer greater patient convenience. The role of capecitabine as a replacement for intravenous fluorouracil in combination regimens is under investigation. 

Capecitabine is a prodrug, which is activated by several enzymatic steps to produce active fluorouracil within the body. Because allopurinol is reported to modulate fluorouracil, with possible decreased efficacy (see... 

Hsu CH, Yang TS, Hsu C, Toh HC, Epstein RJ, Hsiao LT, Chen PJ, Lin ZZ, Chao TY, Cheng AL. Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced... 

Capecitabine is a tumor-selective oral fluoropyrimidine. It has been approved by the FDA and NICE for the treatment of colorectal cancer in both the adjuvant and metastatic settings and for patients with breast cancer after anthracycline and taxane therapy [93 ,94 ]. It has also been approved by NICE for advanced gastric cancer as part of platinum-based therapy [95 ]. In a randomized phase III study of adjuvant capecitabine versus fluorouracil -I- leucovorin, efficacy was similar between the groups but grade 3/4 adverse reactions were significantly less common in those who were given capecitabine [96 ]. The starting dose is usually 1000-1250 m m bd for 14 days, followed by 7 days rest. 

Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, Viens P, Cai C, Mullaney B, Peck R, Hortobagyi GN. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol 2007 25(23) 3407-14. 

Placebo-controlled studies In a double-blind, randomised study including 106 participants, the efficacy of pyridoxine therapy in preventing the use of capecitabine dose modifications for treatment of hand and foot syndrome in patients with colorectal or breast cancers was evaluated. After 12 weeks of treatment, pyridoxine therapy was associated with a trend towards reduction in progression free suroival, with no significant effect on objective response rate [17 j. 

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