The successful treatment of 5-fluorouracil (5-FU) overdose in a patient with malignancy and HIV/AIDS with uridine triacetate.

According to the NIH, about 275000 patients receive treatment with 5-Fluorouracil (5-FU) and more than 1300 die from 5-FU toxicity every year from life-threatening myelosuppression, gastrointestinal complications, and neurotoxicity. Immunocompromised persons are at higher risk of developing toxicity. Recently uridine triacetate (Vistagard®) has been approved by the Food and Drug Administration (FDA) as the only specific antidote available for 5-FU poisoning. In a clinical trial (n=135), 96% of patients with 5-FU toxicity recovered after treatment, where as in a historical control group only 10% survived. This is the first published case report of survival after 5-FU overdose who also was immunocompromised from HIV/AIDs. A 52year old male with history of HIV/AIDS (CD4 70), CNS toxoplasmosis and anal cancer presented to the emergency department after realizing he had received an entire course of 5-FU in 24 instead of 96h. Treatment with uridine triacetate was arranged in the emergency department. After receiving treatment the patient was asymptomatic and had an uncomplicated hospital course. 5-FU poisoning must be recognized early as uridine triacetate is approved by the FDA for use within 96h following the end of 5-FU administration. Emergency medicine physicians should promptly recognize and treat 5-FU poisoning. However, this may be challenging as patients may not seek medical attention until many hours or several days after last administration since symptoms are often delayed with 5-FU poisoning.

[YAKTON INFLUENCE ON THE RABBITS CARDIAC ACTIVITY AND SYSTEMI HEMODYNAMIC IN THE CONDITIONS OF 5-FLUOROURACILUM INTOXICATION].

In the experiments on the rabbits the disturbances of cardio and systemic hemodynamic after 5-fluorouracilum administration have been shown. Yakton administercd intravenously in dose 560 mg/ kg one hour before 5-fluorouracilum protects the disturbances of cardio- and systemic hemodynamic data in animals.

Courage, collaboration, complexity and chemotherapy safety: the view from the sharp end.

The Canadian oncology community was devastated by the news in August 2006 that a patient had died from an overdose of fluorouracil. Where we once thought our checks and balances ensured patient safety, we now knew they were not enough. Practice immediately began to change around the country. However, the incident report highlighted that there was much we still didn't know about safety issues in intravenous ambulatory chemotherapy safety in Canada. In response, an interdisciplinary, pan-Canadian team launched an 18-month exploratory study, resulting in a report identifying several safety issues and associated recommendations. This paper summarizes the key insights we have gathered for Canadian oncology nurses in being part of this study: that we need courage to come forward and disclose safety concerns; we should collaborate to come up with safety improvements that work for everyone; and we should strive to simplify our work at the sharp end by reducing complexity upstream and throughout the system.

5-Fluorouracil toxicosis in the dog.

Twenty-six cases of accidental 5-fluorouracil (5-FU) ingestions by dogs were reviewed from phone calls to the Illinois Animal Poison Information Center. Cases were collected from January 1, 1987 to December 31, 1988. Of the 26 calls involving 5-FU exposures, 12 were classified as "toxicosis," 13 as "suspected toxicosis," and one as "exposure." Dogs were the only species involved in 5-FU cases received during this time. Accurate estimates of the amount of 5-FU ingested by dogs could be made in 17 cases. Ingestion of more than 20 mg/kg of 5-FU was associated with the development of toxicosis. None of the 12 dogs that ingested oral doses in excess of 43 mg/kg (estimated) survived. Clinical signs associated with 5-FU poisoning in the dog were death, seizures, vomiting (with and without blood), tremors, diarrhea (with and without blood), ataxia, and depression. Clinical signs generally developed within 45 to 60 minutes after exposure, and deaths occurred 6 to 16 hours after ingestion.

[Cardiac toxicity of 5-fluorouracil. Two cases]. / Cardiotoxicité du 5-fluorouracile. Deux observations.

Major ventricular repolarization disorders without evidence of myocardial infarction developed in 2 patients during the first course of a 5-fluorouracil (5-FU) treatment in doses of 1,000 mg/m2/day. Anginal pain was present in one patient but not in the other. The electrical abnormalities persisted for more than 6 weeks in one case. Explorations carried out 2 and 6 weeks later respectively under calcium inhibitors showed absence of coronary artery stenosis, negative methyl ergonovine test (even after 5-FU infusion in one patient) and normal left ventricular kinetics. The mechanism of cardiac toxicity is discussed on the basis of these data: some elements support a coronary spasm and others direct myocardial toxicity.

Use of uridine triacetate for the management of fluorouracil overdose.

PURPOSE: The use of uridine triacetate for the management of fluorouracil toxicity is reported. SUMMARY: A 55-year-old man with malignant neoplasm of the sigmoid colon (stage IIIC) was seen in an outpatient chemotherapy center for his first six-month regimen of leucovorin calcium, fluorouracil, and oxaliplatin. Fluorouracil 2400 mg/m(2) i.v. was prescribed to be given over the next 46 hours at a home infusion center. Due to a medication error, a home infusion pharmacist incorrectly programmed the 46-hour infusion of fluorouracil to be administered over 4 hours. To manage the fluorouracil overdose, the physician decided to start the patient on uridine triacetate. The patient received his first dose of uridine triacetate 18 hours after the fluorouracil overdose. He was admitted to the hospital for observation and daily laboratory tests during treatment with uridine triacetate. He received ondansetron (as the hydrochloride salt) 8 mg orally 20 minutes before each dose of uridine triacetate to prevent nausea and vomiting. Uridine triacetate 11 g every 6 hours was administered orally for a total of 20 doses. It was mixed with applesauce at the time of administration and followed with 8 oz of water. The patient's laboratory values remained stable. The patient did not experience any nausea or vomiting during treatment. He was discharged from the hospital on day 5, with no clinical complications and an Eastern Cooperative Oncology Group Performance score of 0. CONCLUSION: A patient with colon cancer who had received an overdose of fluorouracil was successfully treated with a five-day course of oral uridine triacetate.

5-fluorouracil toxicity with severe bone marrow suppression in a dog.

This report describes 5-fluorouracil (5-FU) toxicity in a dog that resulted in severe bone marrow suppression. The dog initially was presented with neurologic and gastrointestinal signs and developed pancytopenia characterized by severe neutropenia and thrombocytopenia. Examination of bone marrow aspirate showed aplasia. The dog also had marked echinocytosis, which has been previously associated with in vitro 5-FU exposure. The patient was given aggressive supportive care and recovered within 25 d of exposure. To the authors' knowledge, this is the first report of a case of 5-FU toxicity in a dog to include results of bone marrow examination, as well as the first to describe echinocytosis related to 5-FU toxicity.

New formulation of 5-fluorouracil in microspheres reduces toxicity in mice.

A new dosage formulation of 5-fluorouracil incorporated in microspheres (5-FU-MS) was developed for the treatment of peritoneal carcinomatosis. We studied the acute toxicity and side effects of i.p. 5-FU-MS in mice. The 50% lethal dose value for 5-FU-MS was 535.4 mg/kg of 5-FU, which was 2.22 times that of the aqueous 5-FU solution. Deaths occurred 12-17 days after the administration of 5-FU-MS, but within 11 days after the administration of aqueous 5-FU. Thus, lethal toxicity appeared later with 5-FU-MS than with aqueous 5-FU. There were no differences in pathologic findings on autopsy between mice given the two dosage formulations.

Immunopotentiating activity of nigerooligosaccharides for the T helper 1-like immune response in mice.

The immunopotentiating activity of nigerooligosaccharides (NOS), a mixture of nigerose, nigerosyl glucose and nigerosyl maltose, was studied in vitro and in vivo in mice. Mitogen-induced proliferation of splenocytes from normal mice was augmented in a dose-dependent manner by nigerose of NOS. NOS enhanced interleukin 12 (IL-12) and interferon-gamma (IFN-gamma) production by normal splenocytes in the presence of the potent IL-12 inducer, heat-killed Lactobacillus plantarum L-137, in vitro. Consistent with the in vitro finding, L. plantarum L-137-induced IL-12 production and IL-2-induced IFN-gamma production were augmented in mice fed with a 14.6% NOS diet for 2 weeks compared with mice fed with a control diet. Notably, mice fed with the NOS diet showed significantly longer survival time than the control mice after the induction of an endogenous infection by administering 5-fluorouracil in a lethal dose. Taken together, these results suggest that NOS may exert immunopotentiating activity through the activation of an IL-12-dependent T helper 1-like immune response.

Experimental neurotoxicity of 5-fluorouracil and its derivatives is due to poisoning by the monofluorinated organic metabolites, monofluoroacetic acid and alpha-fluoro-beta-alanine.

Two metabolites of 5-fluorouracil (FU), monofluoroacetic acid (FA) and alpha-fluoro-beta-alanine (FBAL), were continuously administered into the left ventricle of the brain in cats for up to 1 month to investigate the mechanism of neurotoxicity of FU and its derivatives. The cumulative doses of FU and FBAL over a 1-month period were 1.5-45 mg (20 cats) and 0.2-4.8 mg (21 cats), respectively. As controls for each experimental group, acetic acid (AA) and beta-alanine (BAL) were administered. In terms of survival time in relation to the cumulative dose and molecular weight, FBAL was more toxic than FA. Neuropathologically, two types of change, vacuoles and necrosis/softening-like change, were found. The vacuoles were 20-50 microns in diameter, and distributed mainly in the cerebellar nuclei, white matter and the tectum and tegmentum of the brain stem in both experimental groups. Electron microscopically, these vacuoles were due to splitting of the myelin intraperiod line or separation between the axon and the innermost layer of myelin. Necrosis/softening-like change occurred preferentially in the FBAL group and was located symmetrically in the superior and inferior colliculi, oculomotor nuclei and thalamus. Both types of neuropathological change, especially those in the FBAL group, were similar to those found in cats orally administered with FU and its derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)