Capecitabine metastatic

Capecitabine was clinically first approved for the co-treatment of refractory metastatic breast cancer. Its therapeutic spectrum has been expanded to include metastatic colorectal cancer, and there are hopes that it might broaden further as positive results of new clinical trials become available. Capecitabine, thus, affords an impressive gain in therapeutic benefit compared to 5-FU due to improved oral bioavailability and relatively selective activation in and delivery to tumors. 

Approval Letter The drug is approved. An example of the approval news for Tykerb, a kinase inhibitor in combination with capecitabine for the treatment of advanced or metastatic cancer, is presented in Exhibit 8.3. 

Thomas ES, Gomez HL, Li RK, Chung H-C, Fein LE, Chan VF, Jassem J, Pivot XB, KJimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat FT, Roche HH. (2007). Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol 25 5210-5217. 

Van Cutsem E, Twelves C, Cassidy J et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer results of a large phase III study. J Clin Onco/2001 19 4097 106. 

Although not a taxane, ixabepilone is a novel microtubule inhibitor that was recently approved for metastatic breast cancer in combination with the oral fluoropyrimidine capecitabine or as monotherapy. It is a semisynthetic analog of epothilone B, and is active in the M phase of the cell cycle. This agent binds directly to 6-tubulin subunits on microtubules, leading to inhibition of normal microtubule dynamics. Of note, this agent continues to have activity in drug-resistant tumors that overexpress P-glycoprotein or tubulin mutations. The main adverse effects include myelosuppression, hypersensitivity reactions, and neurotoxicity in the form of peripheral sensory neuropathy. 

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... 

In summary, capecitabine (1), an A -carbamate pyrimidine nucleoside prodrug of cytotoxic antimetabolite 5-fluorouracil, is an FDA-approved anticancer drug that can be administered orally. This compound uses a multilayer of prodrug strategies that not only avoids side effects arising from exposure of toxic metabolites to healthy tissue but is converted to 5-fluorouracil only by enzymes preferentially expressed in many cancer cell types, thus resulting in selective delivery of the drug to tumors. Capecitabine is marketed under the trade name of Xeloda for use in the treatment of metastatic colorectal and breast cancers and metastatic breast cancer that is resistant to paclitaxel or anthracycline therapies. 

Capecitabine [cape SITE ah bean] is a novel oral fluoropyrimidine carbamate. It was approved in 1999 for the treatment of metastatic breast cancer that is resistant to first line drugs [for example, pacli-taxel (see p. 391) and anthracyclines], and is currently also used for treatment of colorectal cancer. 

Every Monday in your oncology outpatient department, you run a pharmacist/ nurse-led oral capecitabine clinic, where patients are referred to you by oncologists for pretreatment counselling, drug history-taking and supplementary chemotherapy prescribing (under set clinical management plans) for the adjuvant treatment of colon cancer or treatment of metastatic colorectal cancer. 

NICE (National Institute for Health and Clinical Excellence) (2003) Guidance on the use of capecitabine and tegafur with uracil for metastatic colorectal cancer. Technology Appraisal 61. Available at http //www.nice.org.uk/nicemedia/pdf/61Capecitabine CRCfullguidance.pdf [Accessed 4 July 2008]. 

Miller, KD, Chap, LI, Flolmes, FA. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol, 23 792-9, 2005. 

Zarate R, Rodriguez J, Bandres E et al (2010) Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC) a dose-finding study and pharma-cogenomic analysis. Br J Cancer 102 987-994... 

Michaud LB, Gauthier AM, Wojdylo JR, et al. Improved therapeutic index with lower dose capecitabine in metastatic breast cancer (MBC) patients (Pts) (Meeting abstract). Proc Am Soc Clin Oncol 2000 A402. 

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. 

Both irinotecan and oxaliplatin have been combined with capecitabine and preliminary data suggest these combinations will be safe and effective in the initial treatment of metastatic colorectal cancer. The current FDA-approved indication for capecitabine is... 

Miscellaneous Salvage Chemotherapy. Similar to initial treatment of metastatic colon cancer, capecitabine is being investigated as a replacement for infusional fluorouracil in salvage regimens in combination with irinotecan or oxaliplatin. Initial results from small trials suggest that this will be a safe and effective way to treat refractory disease. 

Patt YZ, Lin E, Leibman J, et al. Capecitabine plus irinotecan for chemotherapy nai ve patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 2003 22 281 (Abstract 1130). 

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