Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-four consecutive patients with metastatic breast carcinoma (MBC) refractory to first line chemotherapy were treated with high-dose folinic acid (FA) 100 mg/m2 diluted in 250 cc of normal saline as 2 hour infusion followed by 5-fluorouracil (5FU) 400 mg/m2 bolus then 5FU 600 mg/m2 as continuous infusion for 22 hours. This therapy was repeated for 2 consecutive days. Chemotherapy was repeated every 15 days. All enrolled patients were evaluable for objective response. A complete response was achieved in 1 patient (4%) and a partial response in 6 cases (25%) for an overall response rate of 29% (confidence limits 18%-39%). The median duration of objective responses was 8.4+ months (range 3.0+/12.8). Six patients showed no change (25%) with a median duration of 4.0 months 11 patients progressed (46%). A subjective improvement in tumor-related symptoms was reported by all responding patients and in 3 patients with no change. Most patients (7/10) with symptomatic bone lesions had a subjective improvement with reduction in analgesic drugs consumption. Objective responses were observed at all sites of disease. In fact, responses were seen in the skin liver lung bore and rodal metastases. The median overall survival was 13.0+ months (range 4.0/16.2+). Over a total of 160 cycles (a mean of 6.6 cycles/patient) grade 1-2 leukopenia was seen in 9 patients (37%) grade 1 thrombocytopenia in 4 patients (17%) and grade 1 anemia in only 2 cases (8%). Grade 3-4 leukopenia or thrombocytopenia were not seen. Phlebitis at the injection vein occurred in 3/10 patients (30%) which refused to implant a central line. In patients with a central line or a port-a-cath no cases of vascular, toxicity were seen. Gastrointestinal toxicity was very mild with 9 patients (37%) suffering from grade 1-2 nausea/vomiting 6 patients (25%) complaining of grade 1-2 diarrhea and 6 patients with grade 1-2 stomatitis. Hand-foot syndrome was observed in only 1 patient. No cases of grade 3-4 gastrointestinal toxicities have been, observed. No cases of cardiotoxicity and/or neurotoxicity were recorded. The combination of high-dose FA and 5FU given as 48 hour continuous venous infusion every 2 weeks is active, at least in terms of objective response rate and tumor-related symptoms palliation against anthracycline-refractory MBC. These results compare favorably with bolus administration of FA and 5FU or other salvage regimens.
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PMID:Treatment of refractory metastatic breast cancer with 5-fluorouracil and levofolinic acid as 48 hours continuous venous infusion. 1047 46

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.
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PMID:Management of adverse events and other practical considerations in patients receiving capecitabine (Xeloda). 1534 79

We evaluated the effect of capecitabine for metastatic breast carcinoma. Of 18 metastatic breast carcinoma patients experienced in our institution from November 2002 to July 2007, all patients had resisted the anthracycline or taxanes therapy before. Of these patients, 7 had liver, 6 had bone, and 5 had lung metastases. The capecitabine response in these 18 patients was evaluated as follows: PR in 4, long SD in 6, SD in 3, and PD in 5. In particular, 3 patients with liver metastases showed remarkable tumor regression. Compared to the 3rd-and 4th-line, 2nd-line capecitabine proved more effective. Hand-foot syndrome was found in 4 patients. Only one patient discontinued the therapy due to nausea. These results showed that capecitabine may be a useful treatment regimen for chemotherapy-resistant metastatic breast carcinoma patients.
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PMID:[Clinical effect and positioning of capecitabine for metastatic breast carcinoma]. 1870 41

5-Fluorouracil (5-FU) is an antimetabolite that acts during the S phase of the cell cycle. The active metabolite, 5-fluorodeoxyuridine monophosphate inhibits thymidylate synthase (TS), thus preventing DNA synthesis, which leads to imbalanced cell growth and ultimately cell death. 5-FU and its oral prodrug capecitabine are used in the treatment of a number of solid tumors, including colorectal, breast, gastric, pancreatic, prostate, and bladder cancers. Common side effects include leukopenia, diarrhea, stomatitis, nausea, vomiting, and alopecia. Hand-foot syndrome (HFS) is a relatively common side effect of cytotoxic chemotherapy. It is more frequently associated with 5-FU, capecitabine, and cytarabine. This article reports on the case of a 55-year-old black man with metastatic colorectal carcinoma that was refractory to recommended treatment measures who developed grade 3 HFS after treatment with modified FOLFOX6 (leucovorin [LV]/5-FU/oxaliplatin) and bFOL (bolus 5-FU/LV/oxaliplatin) regimens. Treatment was discontinued despite excellent response to chemotherapy. The patient had progression of disease on IROX (irinotecan/oxaliplatin) and irinotecan/cetuximab regimens. He was started on gemcitabine/capecitabine and developed HFS again, which was controlled with aggressive skin care and vitamin B6 treatment. Full sequencing of the dihydropyrimidine dehydrogenase (DPYD) gene and analysis of the human TS gene (TYMS) promoter region was performed. Pharmacogenetic testing revealed 2R/2R genotype of TYMS gene, which is associated with up to a 2.5-fold risk of toxicity to 5-FU therapy. Hand-foot syndrome has proven to be a dose-limiting toxicity of 5-FU, especially of capecitabine, leading to significant morbidity. Hand-foot syndrome seems to be dose dependent, and both peak drug concentration and total cumulative dose determine its occurrence. Genetic variations such as polymorphic abnormality of TYMS are potential causative factors for a significant portion of serious adverse reactions to 5-FU-based therapy.
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PMID:Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: A challenge or a dilemma? 1982 15