Patients and methods eligible patients in this singlearm, openlabel phase ii study received eribulin mesylate. The interpatient variability in the cmax and auc of 5fu was greater than 85%. The methyl group at o6site is removed by the dna repair enzyme mgmt. Review side effects, drug interactions, and pregnancy safety information. In some cases, health care professionals may use the trade name xeloda when referring to the generic drug name capecitabine. Capecitabine is an oral medication for treating advanced breast cancer that is resistant to combination therapy with the drugs of choice, paclitaxel taxol and a drug from the anthracycline family of drugs, for example, doxorubicin adriamycin. Over the past 20 years, increased understanding of the mechanism of action of 5fu has led to the development of strategies that. Capecitabine is converted into fluorouracil by a series of enzymatic reactions. Purpose this phase iii randomized trial clinicaltrials. Capecitabine is the generic name for the trade name drug xeloda. Please see full prescribing information for additional important safety information.
Rarely, this has happened within 1 month after capecitabine was stopped. Capecitabine is an anticancer antineoplastic or cytotoxic chemotherapy drug. Xeloda capecitabine tablets, for oral use initial u. Studies on the mechanism of action of 5fu have not been performed for this application. November 2019 updated mechanism of action and pharmacokinetics, adverse effects, pregnancy and lactation and interactions sections and emetic risk category. Highlights of prescribing information these highlights do not include all the information needed to use capecitabine tablets safely and effectively. Risk factors include patients over 60 years of age and cancer. Lancet 2017 jan 24 adding capecitabine to gemcitabine significantly improved overall survival, establishing the combination as a new standard of care. Bevacizumab in combinations with capecitabine is not recommended within its marketing authorisation for the firstline treatment of metastatic breast cancer, that is, when treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate, or when taxanes or anthracyclines have been used as part of adjuvant treatment in the previous. Gemcitabine, sold under the brand name gemzar, among others, is a chemotherapy medication used to treat a number of types of cancer. Alterations in anticoagulant effects altered coagulation parameters e.
Based on findings in animal reproduction studies and its mechanism of action, xeloda can cause fetal harm when administered to a pregnant woman. Find patient medical information for capecitabine oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Gemcitabine plus capecitabine for resected pancreatic cancer. Capecitabine was noninferior to 5 fluorouracil and leucovorin 5fulv for. Capecitabine is metabolized to 5fu via a complex enzymatic pathway.
Capecitabine is a prodrug that is selectively tumour activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase. Based on findings in animal reproduction studies and its mechanism of action, capecitabine can cause fetal harm when administered to a pregnant woman see clinical pharmacology 12. General aspects of drug metabolism and patterns of hepatic injury are discussed separately, as is reactivation of hepatitis b hbv viral infection in patients treated with immunosuppressive therapy, and hepatotoxicity associated with checkpoint inhibitor immunotherapy. It is first metabolized in the liver to 5deoxy5fluorocytidine 5dfcr by carboxylesterase, then to 5deoxy5fluoroudine 5dfur by cytidine deaminase.
Fluorouracil is further metabolized to two active metabolites, 5fluoro2deoxyuridine. Capecitabine is a pyrimidine analogue used as an antineoplastic agent to treat metastatic and advanced forms of breast and colon cancer, often in combination with other agents. Mechanism of action and pharmacokinetics indications and status adverse effects dosing administration guidelines special precautions interactions recommended clinical monitoring supplementary public funding references disclaimer. The mechanism of action of cholestyramine in this situation is unclear. The proposed mechanism of the interaction between capecitabine and warfarin involves downregulation of the cyp2c9 enzyme by capecitabine or its metabolites. More than 50 case reports to date have described capecitabine induced chest pain. Xeloda capecitabine dose, indications, adverse effects. As a prodrug, capecitabine is selectively activated by tumor cells to its cytotoxic moiety, 5fluorouracil. Xeloda capecitabine tablet, film coated genentech, inc. There are many options to minimize or prevent the side effects of capecitabine. Patients and methods women with mbc who had received prior anthracycline and taxanebased therapy were randomly assigned to receive eribulin or capecitabine.
Other common adverse effects include fatigue, hn f o ch3 o n o n h3c o. Capecitabine is a prodrug of 5fu selective tumor activation by thymidine phosphorylase used for the treatment of adenocarcinoma of the colonbreast cancer and causes ataxic gait, leading to a loss of deambulation, which is usually reversible renouf and gill, 2006. Irinotecan and capecitabine have synergistic antitumor activity with distinct mechanisms of action but without overlapping major toxicity. The findings from this study support the use of utidelone plus capecitabine as an effective option for. Capecitabine kap e sye ta been is a pyrimidine analogue pentyloxycarbonyldeoxyfluorocytidine that has antineoplastic action against several solid tumors, including breast and colon cancers. What is capecitabine xeloda, and how does it work mechanism of action. Special pediatric considerations are noted when applicable, otherwise adult provisions apply. Absorption, distribution, metabolism and excretion. However bile acid malabsorption in chemotherapy induced diarrhea is possible and through forming a complex with the bile acids, cholestyramine could shield the already sensitized colonic and ileal. A phase ii study of weekly irinotecan and capecitabine in. Limited available human data are not sufficient to inform the drugassociated risk during pregnancy. Mechanisms of action and clinical strategies daniel b. Gemcitabine, a pyrimidine analog, is structurally similar to cytarabine, but has a wider spectrum of antitumour activity due to its different cellular pharmacology and mechanism of action.
Treatment of capecitabine induced enterocolitis with cholestyramine. Patients with metastatic colorectal cancer mcrc who were taking perifosine plus capecitabine had a median time to progression and survival of 275 weeks and 177 months, respectively, by contrast with 101 weeks and 76 months, respectively, for those taking capecitabine alone. In the 596 patients treated with xeloda as firstline therapy for metastatic colorectal cancer, the incidence of grade 3 or 4 hyperbilirubinemia was similar to the overall clinical trial safety database of xeloda monotherapy. Over the past 20 years, increased understanding of the mechanism of action of 5fu has led to the development of strategies that increase its anticancer activity. These cancers include breast cancer, ovarian cancer, nonsmall cell lung cancer, pancreatic cancer, and bladder cancer. Chemotherapy in patients with anthracycline and taxane. Data from cultured human cancer cell lines indicate that capecitabine becomes cytotoxic only after conversion to 5fu. Capecitabine tabletsusp are indicated as a single agent for adjuvant treatment in, patients with dukes c colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. Highlights of prescribing information these highlights do not include all the information needed to.
Chemotherapy hepatotoxicity and dose modification in. Capecitabine is a fluoropyrimidine carbamate belonging to the class of antineoplastic agents called antimetabolites. Moreover, in vitro data indicate that the combination of capecitabine and temozolomide may have. Capecitabine, sold under the brand name xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer. The mechanism of action of temozolomide involves dna methylation at the o6guanine site. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of her2positive breast cancer. It undergoes threestep enzymatic conversion to become cytotoxic. Capecitabine xeloda, an oral fluoropyrimidine, is a 5fu prodrug drug used in the treatment of female breast cancer and colorectal cancer crc. Treatment of capecitabineinduced enterocolitis with. Patients receiving concomitant xeloda and oral coumarinderivative. Influence of the antacid maalox on the pharmacokinetics of capecitabine in cancer patients. The mechanisms of action, indications, and potential for drug interactions vary for oral chemotherapy. Perifosine and capecitabine in metastatic colorectal.
This has happened within several days and up to several months after capecitabine was started. Phase ii study of the halichondrin b analog eribulin. Mechanism of the antidiarrheal effect of loperamide. Fluorouracil is metabolized in both normal and tumor cells to 5fluoro2. Common side effects include abdominal pain, vomiting, diarrhea, weakness, and rashes. A sdhb malignant paraganglioma with dramatic response to. The mechanism of action of capecitabine is as a nucleic acid synthesis inhibitor. Gemcitabine plus capecitabine for resected pancreatic cancer david h. Capecitabine side effects are often predictable in terms of their onset, duration, and severity. The safety and efficacy of vistogard initiated more than 96 hours following the end of fluorouracil or capecitabine administration have not been established. Alt elevations above 5 times the uln occurred in capecitabine with some blood thinners like warfarin.
Xeloda capecitabine is a drug used to treat breast cancer that has metastasized to other tissues, as well as colon and colorectal cancers that have spread to lymph nodes and other parts of the body. Nct00337103 compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer mbc. Xelodawarfarin interaction see full prescribing information for complete boxed warning. Capecitabine side effects will improve after therapy is complete. For breast cancer it is often used together with docetaxel. Mechanism of action capecitabine, fluoropyrimidine carbamate, is a prodrug of fluorouracil. Capecitabine is a prodrug of 5fluorouracil 5fu and is converted to this active metabolite intracellularly, where it acts by interfering with dna, rna and protein synthesis and inhibiting cell division.
Capecitabine capecitabine tablet, film coated accord healthcare inc. We can confirm the rna and dna synthesis first, and. Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progressionfree survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. Traditional oral chemotherapy agents cause damage to cancer cells by nonspecifically interfering with cellular division. Capecitabine may increase the anticoagulant effects of warfarin increasing the international normalized ratio several days up to several months after initiating capecitabine or within one month after stopping the therapy.
Capecitabine has been designed and developed as a prodrug to the known cytotoxic agent 5fu. One of the enzymes involved in this activation process, thymidine phosphorylase is expressed in higher concentrations in some human carcinomas compared to normal tissues, which may result in higher intratumor concentrations of fluorouracil. We conducted a phase ii study to evaluate the efficacy of weekly irinotecan plus capecitabine in patients with previously treated nonsmall cell lung cancer nsclc. Review of structure, mechanism of action, pharmacology, efficacy and safety of capecitabine, an oral prodrug of 5fu. Based on findings in animal reproduction studies and its mechanism of action, xeloda can cause fetal harm when administered to a pregnant. Phase iii openlabel randomized study of eribulin mesylate.