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Antimetabolites
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In the UK, capecitabine is recommended by NICE for use as an adjuvant for Stage III colon cancer following surgery (monotherapy or combination therapy), metastatic colorectal cancer (monotherapy or combination), first-line treatment of advanced gastric cancer (in combination with a platinum-based regimen), and second-line treatment of locally advanced or metastatic breast cancer (as monotherapy or in combination with docetaxel). Of the general cytotoxic side effects, hand-foot (desquamative) syndrome, and diarrhea are the most prominent. Caution is required in patients with cardiac, liver, or renal disease or diabetes.
Overview of changes in cancer treatment strategies
Published in Susan F. Dent, Practical Cardio-Oncology, 2019
Grace Tang, Christine Brezden-Masley
The antimetabolite 5-flourouracil (5-FU) is used alone or in combination with other regimens for a variety of cancers, including breast, gastrointestinal, head, and neck (29). Capecitabine, its oral prodrug, is used for colorectal and metastatic breast cancer (3,29). Large retrospective studies have suggested an incidence between 1.3 and 4.3% for symptomatic cardiotoxicities in patients receiving these agents (1,29). However, this may be underestimated due to differences in the definition of cardiotoxicity and treatment schedules across studies (29). A systematic review of 30 studies found that the most common cardiac side effects of 5-FU and capecitabine are chest pain, palpitations, dyspnea, and hypotension (29). Serious complications are present in 0%–2% of patients and include myocardial infarction, cardiogenic shock, and cardiac arrest (29). Continuous infusion is associated with a higher risk of cardiotoxicities compared to bolus administration (30). The mechanism of 5FU-induced cardiotoxicity is not completely understood; however, possible explanations include coronary thrombosis, arteritis, vasospasm, direct toxic effects on the heart, interaction with the coagulation system, and autoimmune responses (1,31).
Adjuvant Therapy of Colon Cancer
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Oral fluoropyrimidines, especially capecitabine, are important patient-friendly therapeutic alternatives (no venous port system required). This is particularly true in the case of a decision to use a monotherapy. The results of the NSABP C-06 and the X-ACT studies show that oral fluoropyrimidines are as effective as 5-FU in the adjuvant treatment setting.27,28 There may even be a slight superiority of capecitabine to bolus 5-FU: After a median follow-up of 6.9 years, slightly improved disease-free survival (DFS) (HR 0.88, 95% CI 0.77–1.01, non-inferiority p < 0.0001, superiority p = 0.021) and OS (HR 0.86, 95% CI 0.74–1.01, non-inferiority p < 0.001, superiority p = 0.020) were found in the X-ACT study in favour of capecitabine. This effect was noticed for all subgroups, even in patients over 70 years. Thus, in the case a monotherapy with 5-FU is indicated, capecitabine may be regarded as standard treatment. Compared to a 5-FU bolus regimen, patients undergoing adjuvant therapy with capecitabine suffer significantly less from diarrhoea, stomatitis, neutropenia, nausea, vomiting and alopecia. However, hand-foot syndrome is reported more frequently with capecitabine.28,29
A Systematic Review of the Benefit of B-Vitamins as a Complementary Treatment in Cancer Patients
Published in Nutrition and Cancer, 2022
L. Heilfort, S. Kutschan, J. Dörfler, M. Freuding, J. Büntzel, K. Münstedt, J. Hübner
Two high-dose studies examined whether vitamin B6-intake may reduce the number of dose-changes in the treatment with the chemotherapeutic drug capecitabine (29, 32). They both found no difference between the groups in need for dose modifications (Braik et al. (32): n = 77, vitamin B6: 9/38 patients, placebo: 8/39 patients; Corrie et al. (29) after 12 weeks vitamin B6: 63%, placebo: 77%; P = 0.152). However, Corrie et al. (29) found a longer time until a dose modification in the vitamin B6 arm (P = 0.008). Ota et al. (26) mentioned that patients needed chemotherapy dose modifications or interruption of the administration of capecitabine for different reasons. But the study did not distinguish by what method the patients were distributed among the arms.
Capecitabine in treating patients with advanced, persistent, or recurrent cervical cancer: an active and safe option?
Published in Expert Opinion on Drug Safety, 2021
Federica Tomao, Giuseppe Caruso, Lucia Musacchio, Violante Di Donato, Maria Cristina Petrella, Monica Verrico, Silverio Tomao, Pierluigi Benedetti Panici, Ludovico Muzii, Innocenza Palaia
Valid therapeutic options for platinum-resistant advanced or recurrent cervical cancer patients are lacking. The well-established role of oral capecitabine in the treatment of several cancers, including breast cancer, colorectal cancer, and head and neck cancer has led to an increasing interest in the potential benefit of the use of capecitabine also for patients with cervical cancer. Oral CT offers several advantages over the parenteral route and is becoming an attractive option in oncological practice, especially when no intravenous treatment seems clearly more effective. The easy oral administration offers greater flexibility and convenience and improves the quality of life of patients, while reducing intravenous catheter-related complications (e.g. local skin and bloodstream infections, dislodgment, thrombosis) and the use of health care resources for inpatient and ambulatory patient care services.
A life-threatening drug-drug interaction between capecitabine and brivudine in a patient with metastatic breast cancer
Published in Journal of Chemotherapy, 2019
Angeliki Tsifi, George Papaxoinis, Panagiotis Diamantopoulos, Marina Mantzourani, Vasiliki Antoniadou, Asimina Halioti, Helen Gogas
Capecitabine is an effective antimetabolite that is currently approved for colorectal and breast cancer.4,5 It is an orally administered fluoropyrimidine carbamate activated by thymidine phosphorylase.6 After its oral administration, it is fully absorbed by the intestinal membrane and it is converted in the liver into 5΄-deoxy-5-flourocytidine (5΄-DFCR) by carboxylesterase.6 It is then converted into 5΄deoxy-5-flourouridine (5΄-DFUR) by cytidine deaminase, an enzyme that can be found in most tissues, especially in healthy liver tissue and human tumour tissues.6 Finally, 5΄-DFUR is converted into 5-Fluorouracil (5-FU) by thymidine phosphorylase, which is also an enzyme found in great concentrations in healthy liver tissue and human tumours.6 Thus, 5FU is used as a potent anticancer drug, respecting the healthy tissues and mainly, targeting tumour tissues.6,7 5-FU is subsequently catabolized by dihydropyrimidine dehydrogenase (DPD) and other enzymes into inactive metabolites, or anabolized by thymidine phosphorylase and thymidine kinase into cytotoxic molecules.3–6