Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 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

Effective palliation of metastatic breast carcinoma (MBC) after the failure of front-line chemotherapy for advanced disease, often based on the use of anthracyclines and taxanes, is quite difficult to achieve due to the development of dominant neoplastic cellular clones highly resistant to further therapy. Therefore the therapeutic index of second and third line chemotherapeutic treatments is usually quite low. Thirty patients with MBC with progressive disease after anthracycline-based chemotherapy as first line therapy were treated with l-FA 100 mg/m2/day and 5FU 1000 mg/m2/day ad continuous venous infusion for 96 hours every 4 weeks. Most patients (60%) had multiple sites of disease at entry and had visceral lesions as the dominant site of disease. Twenty-eight patients were evaluated for objective response: two patients had clinically progressive disease before restaging after the third cycle of chemotherapy. These patients were considered progressive disease since all patients were included in an intent-to-treat analysis. Nine patients achieved partial response for an overall response rate of 30% (intent-to-treat analysis) with a median duration of 9.5+ months (range 4.0/14.0 months), and disease stability was obtained in 10 cases (33%) with a median duration of 5.5 months (5-11). Progressive disease was recorded in 9 patients. After a median follow-up of 11 months, the overall median survival time of the whole series of patients was 14.0+ months. Objective responses were recorded both at visceral and bone sites. Chemotherapeutic treatment was generally quite well tolerated. No toxic deaths were recorded. Among gastrointestinal side-effects grade 3 stomatitis was noted in 30% of patients, and grade 3 diarrhea in 10% of cases. Grade 3-4 leukopenia was observed in 23% of patients, but significant episodes of febrile neutropenia were limited (2 patients). Grade 3 thrombocytopenia was seen only occasionally in 1 patient. Grade 1 anemia was recorded in 10% of patients. Hand-foot syndrome was noted in 2 patients (7%). Cardiotoxicity was minimal. The combination of 5FU and high-dose I-FA given as 96 hour continuous venous infusion was active, at least in terms of the overall response rate, against anthracycline refractory metastatic breast carcinoma. These results compare favourably with bolus 5FU/FA or other salvage regimens in terms of antineoplastic activity, and is well tolerated both subjectively and objectively by most patients.
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PMID:Treatment of refractory metastatic breast cancer with 5-fluorouracil plus levofolinic acid as continuous venous infusion: a phase II study. 1062 52

Although 5-fluorouracil (5-FU) was first introduced in 1957, it remains an essential part of the treatment of a wide range of solid tumors. 5-FU has antitumor activity against epithelial malignancies arising in the gastrointestinal tract and breast as well as the head and neck, with single-agent response rates of only 10%-30%. Although 5-FU is still the most widely prescribed agent for the treatment of colorectal cancer, less than one-third of patients achieve objective responses. Recent research has focused on the biomodulation of 5-FU to improve the cytotoxicity and therapeutic effectiveness of this drug in the treatment of advanced disease. As all the anticancer agents, 5-FU leads to several toxicities. The toxicity profile of 5-FU is schedule dependent. Myelotoxicity is the major toxic effect in patients receiving bolus doses. Hand-foot syndrome (palmar-plantar erythrodysesthesia), stomatitis, and neuro- and cardiotoxicities are associated with continuous infusions. Other adverse effects associated with both bolus-dose and continuous-infusion regimens include nausea and vomiting, diarrhea, alopecia, and dermatitis. All these reasons explain the need for more effective and less toxic fluoropyrimidines. In the first part of this review, we briefly present the metabolic pathways of 5-FU responsible for the efficacy and toxicity of this drug. This knowledge is also necessary to understand the target(s) of biomodulation. The second part is devoted to a review of the literature on three recent prodrugs of 5-FU, i.e., capecitabine, UFT (ftorafur [FTO] plus uracil), and S-1 (FTO plus 5-chloro-2,4-dihydroxypyridine plus potassium oxonate). The pharmacological principles that have influenced the development of these new drugs and our current knowledge of the clinical pharmacology of these new agents, focusing on antitumor activity and toxicity, are presented. The literature was analyzed until March 2002. This review is intended to be as exhaustive as possible since it was conceived as a work tool for readers wanting to go further.
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PMID:Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. 1218 93

Although 5-fluorouracil (FU) was first introduced in 1957, it remains an essential part of the treatment of a wide range of solid tumors. FU has antitumor activity against epithelial malignancies arising in the gastrointestinal tract, breast as well as the head and neck, with single-agent response rates of only 10-30%. Although FU is still the most widely prescribed agent for the treatment of colorectal cancer, less than a third of patients achieve objective responses. Recent research has focused on the biomodulation of FU to improve the cytotoxicity and therapeutic effectiveness of this drug in the treatment of advanced disease. As all the anticancer agents, FU leads to several toxicities. The toxicity profile of FU is schedule dependent. Myelotoxicity is the major toxic effect in patients receiving bolus doses. Hand-foot syndrome (palmar-plantar erythrodysesthesia), stomatitis, neuro- and cardiotoxicity are associated with continuous infusions. Other adverse effects associated with both bolus-dose and continuous infusion regimens include nausea and vomiting, diarrhea, alopecia and dermatitis. All these reasons explain the need of more effective and less toxic fluoropyrimidines. In the first part of the review, we briefly present the metabolic pathways of FU responsible for the efficacy and toxicity of the drug. This knowledge is also necessary to understand the target(s) of the biomodulation. The second part is devoted to a review of the literature on the various prodrugs of FU, including 5'-deoxy-5-fluorouridine, capecitabine, BOF-A2, ftorafur, UFT, and S-1. The promising approach of gene directed enzyme-prodrug therapy is also presented. A brief survey of antibody directed enzyme-prodrug therapy and some new FU prodrugs concludes the paper. The pharmacological principles that have influenced the development of these new drugs and our current knowledge of the clinical pharmacology of these new agents, focusing on antitumor activity and toxicity, are presented.
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PMID:The prodrugs of 5-fluorouracil. 1267 47

Hand-foot syndrome (HFS) is a rare adverse reaction to oral fluoropyrimidine TS-1, which contains the dihydropyrimidine dehydrogenase (DPD) inhibitor. We treated a recurrent gastric cancer patient with chronic renal failure who developed grade 2 HFS, grade 2 conjunctivitis and grade 3 stomatitis soon after TS-1 administration. Those symptoms improved with the administration of vitamin B6, topical emollient therapy, and so on. We thought that the continuous elevation of serum 5-FU concentration, due to the accumulation of DPD inhibitor from the renal dysfunction, led to the development of HFS, although the participation of 5-FU metabolites such as F-beta-alanine cannot be ruled out.
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PMID:[A patient with recurrent gastric cancer who developed TS-1 induced hand-foot syndrome]. 1279 5

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

Clinical characteristics and risk factors of hand-foot syndrome were investigated in patients who received capecitabine-containing chemotherapy. Toxicity data were analyzed from 179 patients in 4 prospective clinical trials testing docetaxel/capecitabine/cisplatin in stomach cancer, capecitabine/cisplatin in biliary or stomach cancer, and vinorelbine/capecitabine in breast cancer. Hand-foot syndrome was reported in 116/179 (64.8%) of patients, with grade 3 hand-foot syndrome in 8/179 (4.5%). Hand-foot syndrome first developed within the first 3 chemotherapy cycles in 100/116 (86.2%) patients, with the median onset for all 3 treatment regimens occurring during cycle 2. Because severe reactions were rare, hand-foot syndrome was not a major factor influencing treatment schedule. Risk factor analyses showed that combined use of docetaxel and preceding chemotherapy-related stomatitis were significant risk factors for the development of hand-foot syndrome. Our results suggest that a combined treatment agent and a patient's susceptibility to chemotherapy-related toxicity may increase the risk of capecitabine-induced hand-foot syndrome.
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PMID:Hand-foot syndrome in patients treated with capecitabine-containing combination chemotherapy. 1534 18

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