Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UFT (BMS-200604, Uftoral) is an oral fluoropyrimidine that combines uracil and the 5-fluorouracil (5-FU) prodrug, ftorafur, in a 4:1 molar ratio with single-agent activity in breast and gastrointestinal cancers. In vitro studies have shown that irinotecan downregulates thymidylate synthase (TS) expression in tumour cells, leading to synergy between irinotecan and 5-FU that is maximal when irinotecan is given 24 h prior to 5-FU. Given this observed synergy and the confirmatory clinical activity of combination therapy with 5-FU, leucovorin (LV) and irinotecan, we performed a phase I trial to determine the maximum tolerated doses (MTD) of UFT, LV, and irinotecan. Treatment consisted of irinotecan administered as a 90-min intravenous (i.v.) infusion on day 1 followed by twice daily oral UFT/LV on days 2-15, repeated every 21 days. Initial doses were irinotecan 200 mg/m(2) and UFT 200 mg/m(2)/day, with LV dose fixed at 60 mg/day. 31 patients received a total of 130 cycles of UFT/LV and irinotecan. 3 of 9 patients experienced grade 3/4 diarrhoea at the highest dose level of irinotecan 310 mg/m(2) and UFT 300 mg/m(2)/day. Other toxicities included neutropenia, anaemia, alopecia, nausea/vomiting and fatigue. Further dose escalation was not pursued since this level of toxicity was appropriate for future phase II study. One patient with colorectal cancer experienced a partial response and 9 patients with non-small cell lung, colorectal and gastro-oesophageal junction carcinomas had disease stabilisation lasting 4-26 (median 6) cycles. Methylenetetrahydrofolate reductase (MTHFR) C677T genotype was analysed in peripheral mononuclear cells (PMNs) obtained from 24 patients. 2 patients had the homozygous TT polymorphism and 1 of them had grade 3 diarrhoea at the first dose level. Irinotecan on day 1 followed by a 14-day course of oral UFT/LV beginning on day 2 is well tolerated, and suitable for testing in several tumour types. Doses recommended for further study on this schedule are irinotecan 310 mg/m(2) and UFT 300 mg/m(2)/day, with LV 60 mg/day.
 ...
PMID:Phase I trial of UFT/leucovorin and irinotecan in patients with advanced cancer. 1496 16

UFT (Uftoral), a blend of uracil and Tegafur, is an antitumour agent for oral administration that is presumed to maintain the concentration of 5-fluorouracil (5-FU) in tumour tissue. As a result of increased use of high-dose 5-FU-based chemotherapy for various solid tumours, complicated drug-induced colitis is more frequently observed. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU and its deficiency is responsible for the severe toxicities encountered in cancer patients receiving 5-FU. The authors present the case of a patient with locally advanced temporal bone carcinoma who developed haematochezia during a course of chemotherapy with UFT. Colonoscopy of the patient showed bleeding petechia-like lesions and superficial inflammatory exudate, whilst histology revealed non-specific inflammatory changes of the colon mucosa. As the haematochezia improved with supportive treatment, neutropenia complicated the clinical picture. This patient developed life-threatening UFT toxicity without an exon-14 DPD gene mutation.
 ...
PMID:Severe colitis after administration of UFT chemotherapy for temporal bone carcinoma. 1500 14