A phase II study of combined oral uracil and ftorafur with leucovorin for patients with squamous cell carcinoma of the head and neck

BACKGROUND: The objective of this Phase II study was to define the response rate, safety profile, and toxicity of oral uracil and ftorafur (UFT) with leucovorin (UFT/LV) as a palliative treatment for patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group performance status < 2 and adequate organ function were enrolled in an institutional review board-approved trial. Prior induction or adjuvant chemotherapy was permitted provided 6 months had elapsed since the last chemotherapy. Patients were treated with UFT 300 mg/m(2) per day and leucovorin 90 mg per day administered in three doses daily for 28 days followed by a 7-day break for a 35-day cycle. Planned intrapatient dose modifications were based on individual toxicity. Patients were removed from the study for progression of disease or unacceptable toxicity. RESULTS: One hundred six cycles of UFT/LV had been administered to 42 patients as of January 1, 2000. The most common toxicities, in descending order of incidence, were anemia, pain, fatigue, diarrhea, nausea, mucositis, and anorexia. Clinically significant toxicities attributable to UFT/ LV were primarily gastrointestinal. On an intent-to-treat basis, three patients (7%) achieved a complete response, and six patients (14%) achieved a partial response. The overall response rate was 21% (95% confidence interval, 10--37%). CONCLUSIONS: UFT/LV therapy is feasible in this patient population and is generally well tolerated. Response rates are similar to the rates expected with continuous-infusion 5-fluorouracil. UFT/LV should be studied further both alone and in combination therapy for patients with SCCHN.     

Cholinesterase Inhibitors: Applying Pharmacokinetics to Clinical Decision Making

Background

Cholinesterase inhibitors are indicated for the treatment of Alzheimer-type dementia. There are few direct comparative studies of adverse effects or studies to suggest clinical superiority of one inhibitor over the others.

Objective

The objective of this study was to relate pharmacokinetic differences among the agents to potential clinical considerations.

Methods

Population pharmacokinetics were obtained from US Food and Drug Administration–approved label information and published literature. Plasma concentration–time profiles were derived from these parameters using noncompartmental pharmacokinetic modeling.

Results

Plasma concentration profiles differed significantly among different agents and between different formulations of the same agent.

Conclusions

The initial choice among the various cholinesterase inhibitors requires consideration to adherence and cost. Consideration to differences in pharmacokinetics among these drugs provides a better understanding for the clinical practice of dose titration, identification and management of drug-related side effects, and lapses in therapy. Pharmacokinetic considerations among the various agents and formulations provide the clinician with options to enhance therapy when these agents are chosen for treatment of patients with Alzheimer-type dementia.     

Efficacy of panretinal photocoagulation in central retinal vein occlusion

This retrospective study reviews the efficacy of panretinal photocoagulation in the prevention and management of ocular neovascularization in 55 cases of central retinal vein occlusion. Differentiation of occlusions into ischemic and nonischemic forms is of critical importance, with aggressive laser treatment being warranted in the ischemic variety. The presence of ocular neovascularization may not necessarily imply a grim prognosis.     

Iodinated glycerol-induced hypothyroidism

This report describes an adverse reaction to iodinated glycerol, an organic form of iodine prescribed as a mucolytic-expectorant. In a patient with a previous history of severe potassium iodide-induced hypothyroidism, administration of iodinated glycerol resulted in mild subclinical hypothyroidism. There is one report in the literature of goiter resulting from iodinated glycerol and physicians should be aware of the potential for hypothyroidism with this agent. Iodinated glycerol should be added to the list of iodine-containing organic compounds that interfere with thyroid function.     

Prevalence of ocular hemorrhage in patients receiving warfarin therapy

BACKGROUND: Warfarin, the drug most commonly used for outpatient anticoagulation therapy, has bleeding as its main side effect. The objective of this study was to determine the prevalence of ocular hemorrhage in patients receiving warfarin and to compare it to the prevalence in the general population. METHODS: Patients receiving warfarin therapy who were attending the anticoagulation clinic at a tertiary care hospital in Montreal between October and December 1996 received a flyer inviting them to have their eyes examined to look for "ocular bleeding." Consenting patients were examined for subconjunctival hemorrhage, gross hyphema, and vitreous and retinal hemorrhages through external ocular examination and funduscopic examination with the pupils dilated using direct and indirect ophthalmoscopy. RESULTS: Of the 1225 patients seen at the clinic 126 (10%) agreed to participate. Four patients (3%) were found to have intraretinal hemorrhage at the time of examination. All hemorrhages were visually insignificant. INTERPRETATION: The risk of retinal hemorrhage in patients without preexisting ocular disease, such as retinal neovascularization or choroidal vasculopathy, who are receiving warfarin therapy is so small that it should not deter physicians from prescribing this drug when indicated.     

Cefepime neurotoxicity: case report, pharmacokinetic considerations, and literature review

A 67-year-old woman with diabetes mellitus, chronic renal insufficiency, and recurrent urinary tract infections experienced encephalopathy and myoclonus while receiving cefepime. The adverse drug event was accompanied by elevated cefepime levels and abnormal electroencephalograms. This syndrome resolved after discontinuation of cefepime. Neurotoxicity is a known but possibly underreported adverse event associated with cefepime in patients with renal impairment who receive relatively excessive doses. Most cases reverse on drug cessation. In patients with renal disease, the maintenance dosage should be reduced and the patient monitored for neurotoxicity. Cefepime toxicity should be suspected whenever a patient receiving the drug experiences a change in mental status or myoclonus.     

Toxic interaction between acetazolamide and salicylate: case reports and a pharmacokinetic explanation

Two elderly patients, who were chronically receiving aspirin, developed lethargy, incontinence, and confusion after dosing with acetazolamide. Unbound plasma acetazolamide concentrations were elevated and plasma protein binding was reduced, suggesting an interaction with aspirin. In vitro studies demonstrated a concentration-dependent effect of salicylate on acetazolamide binding to serum proteins. At a therapeutic serum acetazolamide level of 8.0 micrograms/ml, the unbound percentage of acetazolamide in serum was 3.3% and increased to 11.0% and 30.0%, with serum salicylate levels of 200 and 386 micrograms/ml, respectively. Furthermore, the apparent association constant of acetazolamide for binding to serum proteins was decreased by 58% and 86% of its control value at these respective salicylate concentrations. The maximal binding capacity of serum for acetazolamide was not affected by salicylate. Pharmacokinetic studies in four volunteers showed that the plasma protein binding and renal clearance of acetazolamide were significantly reduced during chronic salicylate dosing. Salicylate appears to competitively inhibit the plasma protein binding of acetazolamide and simultaneously to inhibit acetazolamide renal tubular secretion. Caution is advised when acetazolamide and salicylate are used concurrently.