Intravenous prophylaxis for paclitaxel-related hypersensitivity reactions.

Severe hypersensitivity reactions to paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were reported during early phase I trials. A premedication regimen consisting of oral steroids 12 and 6 hours before treatment with paclitaxel as well as immediate infusion of diphenhydramine and cimetidine (or ranitidine) before paclitaxel markedly decreased the incidence of hypersensitivity reactions. Subsequently, investigators at the Fox Chase Cancer Center used intravenous dexamethasone, diphenhydramine, and cimetidine immediately before paclitaxel in an effort to obviate the inconvenience of oral steroid administration. Two prospective clinical trials that use carboplatin and paclitaxel were performed in patients with ovarian cancer and in patients with non-small cell lung cancer. In both these trials, all premedication for hypersensitivity reactions was administered intravenously immediately before paclitaxel. No significant hypersensitivity reactions were reported in these two trials, and, subsequently, a large retrospective search of a computerized pharmacy database concluded that a single-dose regimen of intravenous dexamethasone, diphenhydramine, and cimetidine is a safe and convenient alternative for prevention of hypersensitivity reactions associated with outpatient paclitaxel administration.

Acute encephalopathy attributed to 5-FU.

Acute encephalopathy attributable to 5-fluorouracil (5-FU) is rare. A patient experienced this reaction associated with a continuous 5-FU infusion. The etiology of the event remains uncertain, but it is generally reversible and does not preclude retreatment with 5-FU at reduced dosages. Steroids and thiamine may expedite neurologic recovery.

Short-course intravenous prophylaxis for paclitaxel-related hypersensitivity reactions.

PURPOSE: To estimate the incidence of hypersensitivity reactions using a short-course intravenous prophylactic regimen in patients receiving outpatient therapy with paclitaxel. PATIENTS AND METHODS: Patients were identified from a retrospective search of a computerized pharmacy database covering a two-year period from January 1994 through December 1995. Eligible outpatients received paclitaxel as a one- to three-hour infusion 30 minutes after intravenous dexamethasone (10 or 20 mg), diphenhydramine (50 mg), and cimetidine (300 mg) or ranitidine (50 mg). Charts from all patients were then manually reviewed to verify drug administration and to record any evidence of hypersensitivity reactions during the first two cycles of therapy. RESULTS: A total of 283 outpatients were identified from the pharmacy database and all charts reviewed. All patients received intravenous dexamethasone (5 to 20 mg) 30 minutes prior to paclitaxel without prior oral dexamethasone. Hypersensitivity reactions were documented in 13 patients (4.6%) during the first or second cycle with a 95% confidence interval (CI) of 2.2% to 7.0%. Reactions resolved rapidly without sequelae and did not require hospitalization. Only two reactions (0.7%) were graded as serious with a 95% CI of 0.2% to 1.2%, based on the use of bronchodilators and presence of angioedema. Therapy was continued with modification in 10 patients without recurrent hypersensitivity reaction. Therapy was discontinued in two patients without rechallenge and discontinued in one patient after rechallenge with a recurrent hypersensitivity reaction. CONCLUSION: A short-course single-dose regimen of intravenous dexamethasone, diphenhydramine, and cimetidine (or ranitidine) offers a safe and convenient alternative for prevention of hypersensitivity reactions associated with outpatient paclitaxel administration.

A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.

The ability of perioperative cefazolin to reduce the incidence of postoperative wound infection in patients undergoing ablative surgical treatment for carcinoma of the breast was tested in this prospective, randomized, double-blinded study. From May 1983 until December 1985, 118 women were divided into two groups at random. Group 1 consisted of 59 patients and received cefazolin and group 2 was made up of 59 patients who received a placebo. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. Three infections occurred among those in group 1 and five among those in group 2 (p = 0.72). The time to onset of infection was delayed in the patients in group 1 versus those in group 2 (17.7 days versus 9.6 days, p = 0.04). Six of eight infections occurred in patients in whom an interval between biopsy and definitive surgical treatment was present. Prophylactic antibiotics in mammary operations did not reduce postoperative wound infections in this study.

Altered gentamicin pharmacokinetics during the perioperative period.

The effect of surgery on the pharmacokinetics of gentamicin sulfate in hospitalized patients was studied. Patients with cancer undergoing surgery of the head and neck were given gentamicin sulfate in doses calculated to achieve peak serum concentrations of 6-8 micrograms/mL and trough concentrations of 1-2 micrograms/mL. Each patient received a loading dose at the time of surgical incision, followed by five maintenance doses at eight-hour intervals. Steady-state peak and trough serum gentamicin concentrations were predicted using a one-compartment open pharmacokinetic model and literature values for volume of distribution (V) and first-order elimination rate constant (k). Serum gentamicin concentrations were measured 0.25 hours before and at 0.5, 3.5, and 6.5 hours after completion of infusion of the second maintenance dose. Peak and trough serum concentrations were obtained by extrapolation from these measured concentrations using weighted, nonlinear least squares regression. Predicted versus measured serum gentamicin concentrations and estimated versus observed values for V and k were compared. Eight men and seven women had evaluable serum gentamicin concentrations. Patients received a mean calculated maintenance dose of 4.4 +/- 0.7 mg/kg/day. Mean extrapolated peak and trough serum gentamicin concentrations were significantly lower than predicted, and observed values of V and k were significantly greater than estimated values. Gentamicin dosages calculated using standard pharmacokinetic variable values may not produce therapeutic concentrations in patients undergoing surgery. Monitoring of serum concentrations with dosage adjustment when indicated is necessary for optimal therapy in these patients.