Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the long clinical history of 5-FU in gastrointestinal cancer, the development of oral agents has been a productive endeavor, and oral fluoropyrimidine agents are likely to play an important role in the management of colorectal cancer. Results of recent trials in advanced/metastatic colorectal cancer have shown equivalence of response rates, time to disease progression, and median survival and reduced rates of neutropenia and stomatitis with oral capecitabine (Xeloda) or UFT/leucovorin compared with standard fluorouracil (5-FU)/leucovorin regimens. Evaluation of these oral agents in adjuvant therapy, in combination chemotherapy, and in combination with radiation therapy is ongoing.
 ...
PMID:Role of oral chemotherapy in colorectal cancer. 1119 16

Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.). Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles. Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events. Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression. Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients. Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV. In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with an oral home-based therapy patients receiving capecitabine needed more frequent unscheduled home, day care, office and telephone consultations with physicians. In the light of clinical results from the phase III trial demonstrating increased efficacy in terms of response rate, equivalent time to progression (TTP) and survival (OS), and a superior safety profile, the results from this medical resource assessment indicate that capecitabine treatment of colorectal cancer patients results in a substantial resource use saving relative to the Mayo Clinic regimen of 5-FU/LV. This benefit is derived principally from the avoidance of hospital visits for i.v. drug administration, less expensive drug therapy for the treatment of toxic side-effects, and fewer treatment-related hospitalisations required during the course of therapy for adverse drug reactions in comparison to patients treated with 5-FU/LV.
 ...
PMID:Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. 1129 Apr 35

Capecitabine (Xeloda) is an oral prodrug that is enzymatically converted to fluorouracil (5-FU) within cancer cells. Data from two large phase III trials performed in patients receiving first-line chemotherapy for metastatic colorectal cancer showed that capecitabine yielded higher objective response rates and equivalent median time to tumor progression and overall survival rates as 5-FU/leucovorin. In these studies, capecitabine demonstrated lower rates of diarrhea, stomatitis, nausea, and severe neutropenia than bolus 5-FU/leucovorin, but a higher rate of hand-foot syndrome and hyperbilirubinemia. The natural extension of this work has been to evaluate substitution of capecitabine for 5-FU/leucovorin in combination chemotherapy trials with irinotecan (CPT-11, Camptosar) or oxaliplatin (Eloxatin). This is especially important due to concerns regarding toxicities observed with regimens that combine bolus 5-FU/leucovorin with irinotecan or oxaliplatin. Phase I/II and phase II trials of capecitabine in combination with irinotecan or oxaliplatin in patients with advanced disease indicate that the combinations are well tolerated and produce response rates that are in the range of those that would be expected with infusional 5-FU/leucovorin combined with irinotecan or oxaliplatin. Phase III trials have been initiated in the advanced disease and adjuvant settings and should help determine the efficacy, toxicity, and tolerability of the capecitabine/irinotecan or capecitabine/oxaliplatin combination in direct comparison to intravenous 5-FU/leucovorin and irinotecan or oxaliplatin.
 ...
PMID:Current status of capecitabine in the treatment of colorectal cancer. 1252 Jun 35

Although the anti-neoplastic activity of 5-Fluorouracil (5-FU) is improved by continuous infusion or biochemical modulation, the need for in-dwelling central venous catheters and toxicity have proved to be major impediments. Capecitabine (Xeloda, N4-pentyloxycarbonyl-5'-deoxy-5-fluoro-cytidine), an oral fluoropyrimidine, has been synthesized in the laboratory as an inactive precursor that passes intact through the intestinal mucosa and is sequentially converted to 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR) and finally 5-FU in the liver and tumour tissues selectively. Preclinical studies provided evidence of preferential conversion of inactive 5'-DFUR to active 5-FU in solid tumours due to the relative overexpression of the final anabolising enzyme, thymidine phosphorylase (TP), in neoplastic tissues more than in normal counterparts. Phase I/II studies exploring toxicity and the appropriate dosing resulted in the evaluation of the intermittent schedule (2510 mg/m2/day for 14 days every 3 weeks) in subsequent trials. Two large phase III studies in patients with metastatic colon cancer established at least equivalent efficacy and improved tolerability for capecitabine compared to the Mayo Clinic bolus 5-FU/folinic acid regimen. Phase II studies established remarkable activity in women with heavily pretreated metastatic breast cancer. Moreover the combination with a taxane yielded a unique survival benefit compared to the previous gold standard of taxane monotherapy in a phase III trial of women with anthracycline resistant breast cancer. The commonest side-effects are hand and foot syndrome, diarrhoea and stomatitis with serious adverse events occurring in a minority of patients. Myelosuppression was minimal or absent. Toxic manifestations are easily managed with a significant reduction in the frequency of hospitalizations and medical resource use, as shown in appropriate studies. Capecitabine is expected to find a role in the treatment of other tumour types as well as adjuvant administration. It represents an advance in modern drug development, stressing the current shift towards rational development of new agents and home-based outpatient regimens.
 ...
PMID:The rational development of capecitabine from the laboratory to the clinic. 1255 61

One rationale for the development of new treatment strategies for advanced breast cancer is to provide targeted antineoplastic therapy, while at the same time improving the quality of life of patients. One such drug, capecitabine (Xeloda), is an oral fluoropyrimidine 5-fluorouracil carbamate. Capecitabine is converted to 5-fluorouracil primarily in cancer tissue and it has been demonstrated to combine ease of administration, a manageable toxicity profile and potent antineoplastic activity. Capecitabine is widely used in metastatic breast cancer and offers symptom palliation and in combination with docetaxel (Taxotere) improved survival compared with docetaxel alone. Its toxicity profile includes hand-foot syndrome and stomatitis and diarrhea, whereas its hematologic side effects are mild. Capecitabine has been evaluated as a single agent in women with advanced breast cancer where it offers an overall response rate of 20-30%. Capecitabine is synergistic with other chemotherapeutic agents, such as the taxanes, where it increases the response rate to over 40%. This review will place the available data on the use of capecitabine in metastatic breast cancer as a single agent or as part of a combination regime in context.
 ...
PMID:Role of capecitabine (Xeloda) in breast cancer. 1272 73

The oral fluoropyrimidine capecitabine (Xeloda) delivers 5-FU to the tumour site, thereby limiting the side effects and other complications associated with intravenous (i.v.) 5-FU. As an oral drug, capecitabine is preferred to 5-FU by many patients as it can be conveniently taken at home. In first-line metastatic colorectal cancer (MCRC), capecitabine results in superior response rates and equivalent progression-free and overall survival compared with i.v. 5-FU/LV. There is also increasing evidence for replacing i.v. 5-FU with capecitabine in combination with other anticancer agents (e.g. oxaliplatin and irinotecan) in MCRC and in the adjuvant treatment of early stage colon cancer. In anthracycline-pretreated metastatic breast cancer (MBC), adding capecitabine to docetaxel improves survival, time to progression (TTP) and response rates beyond docetaxel. Single-agent capecitabine is also effective in pretreated MBC and is a promising first-line therapy. Capecitabine has a favourable safety profile, the most frequent adverse events being hand-foot syndrome, stomatitis and diarrhoea. Because capecitabine is orally administered, it is possible to intervene promptly with dose interruption/reduction to resolve adverse events without impacting on efficacy. The increasing availability of capecitabine in the home-based setting requires careful consideration of the role of the oncology nurse, who is the key link between the patient and clinician for effective and efficient management.
 ...
PMID:Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. 1534 78

As capecitabine (Xeloda) is converted to 5-FU within tumours it can produce 5-FU-like side effects. However, diarrhoea, stomatitis, nausea, alopecia and neutropenia are significantly less frequent than with i.v. 5-FU. Hand-foot syndrome (HFS) is the only clinical adverse event occurring more often during capecitabine treatment. These findings in MCRC have also been confirmed in a large phase III trial in early stage colon cancer (X-Act adjuvant study) and phase II clinical trials in metastatic breast cancer. Because capecitabine is taken in the outpatient setting, the nurse and/or supervising clinician are responsible for educating patients how to use it correctly and on the nature/recognition/severity of adverse events. Patients need to be aware that temporary interruptions/dose modifications do not reduce the overall efficacy of capecitabine and will most likely lead to a resolution of side effects. Consequently, oncology nurses will be assuming a more significant and pivotal role in the efficient education and support of patients during home-based therapy with capecitabine.
 ...
PMID:Management of adverse events and other practical considerations in patients receiving capecitabine (Xeloda). 1534 79

Many elderly individuals have substantial life expectancy, even in the setting of significant illness. There is evidence to indicate that elderly individuals derive as much survival benefit as younger patients from standard chemotherapy approaches in advanced colorectal cancer. Effective treatments should not be withheld from older patients on the basis of age alone. Treatment decisions should be based on functional status, presence of comorbidities, and consideration of drug-specific toxicities that can be exacerbated in older individuals due to decreased functional reserve. Infusional and weekly fluorouracil (5-FU) regimens are better tolerated than bolus and monthly regimens. Oral capecitabine (Xeloda) reduces the frequency of a number of toxicities compared with bolus 5-FU, including stomatitis, a particularly debilitating toxicity in many elderly patients. The effectiveness and tolerability of oxaliplatin and irinotecan (Camptosar) appear to be similar in older and younger patients. Older patients can also receive bevacizumab (Avastin), although caution is warranted in those with cardiovascular disease. Overall survival in metastatic colorectal cancer improves with the availability of multiple effective chemotherapeutic agents. The full range of effective therapies in advanced colorectal cancer should be extended to elderly patients.
 ...
PMID:Management of advanced colorectal cancer in older patients. 1594 41

Colorectal cancer continues to pose a major public health threat in the United States. Without postsurgical adjuvant therapy, approximately 50% of patients will have recurrent disease and die within five years. Since 1990, five new chemotherapy agents have been added to the therapeutic armamentarium for management of colorectal cancer, and agents traditionally used to treat metastatic and advanced disease increasingly are being applied in the adjuvant setting. One such treatment, capecitabine, offers patients the benefit of oral dosing and permits at-home self-management. A phase III randomized trial, Xeloda in Adjuvant Colorectal Cancer Treatment, demonstrated that treatment with single-agent capecitabine was equivalent to bolus 5-fluorouracil with leucovorin with respect to disease-free survival and overall survival, with significantly less diarrhea, stomatitis, neutropenia, nausea and vomiting, and alopecia. This article reviews the findings and discusses how oncology nurses can help provide effective education and monitoring for patients using oral treatment in the adjuvant setting.
 ...
PMID:Capecitabine: a new adjuvant option for colorectal cancer. 1692 1

The current standard adjuvant chemotherapy for suitable patients with stage III colon cancer is the combination of oxaliplatin and 5-fluorouracil plus folinic acid (5-FU/LV). However, until recently and for many years prior to this, the accepted standard adjuvant chemotherapy was 6-8 months of bolus 5-FU/LV. However, bolus treatment was associated with significant toxicity, namely stomatitis, diarrhea and neutropenia, in addition to multiple hospital visits for drug administration for patients. The X-ACT trial (Xeloda in Adjuvant Colon Cancer Therapy) compared traditional bolus 5-FU/LV (as per the Mayo Clinic regimen) with capecitabine, in the adjuvant treatment of 1987 stage III colon cancer patients. The main safety, efficacy and pharmacoeconomic results have all been published, and the updated 5-year efficacy results have also recently been presented. This trial demonstrated that capecitabine was at least as effective as bolus 5-FU/LV in terms of disease-free and overall survival, with trends towards superiority for both. Moreover, there was much less toxicity associated with capecitabine, apart from hand-foot syndrome which was significantly more prevalent. On the basis of the X-ACT trial, capecitabine was approved by the US FDA, the National Institute for Clinical Excellence and the Scottish Medicines Consortium as monotherapy for the adjuvant treatment of stage III colon cancer.
 ...
PMID:Redefining adjuvant chemotherapy in patients with stage III colon cancer: X-ACT trial. 1840 21


1 2 Next >>