Results of a compassionate-use program using intravenous ondansetron to prevent nausea and vomiting in patients receiving emetogenic cancer chemotherapy.

This study reports the effectiveness and side effects of intravenous ondansetron as a single-agent antiemetic therapy for patients receiving emetogenic cancer chemotherapy under a compassionate-use program for patients not enrolled in controlled clinical trials. Patients were > or = 7 years old and had uncontrolled nausea and vomiting or intolerable side effects with standard antiemetics administered with previous cancer chemotherapy. All patients received ondansetron 0.15 mg/kg every 4 hours x 3 daily doses beginning 30 minutes prior to emetogenic chemotherapy. Patients could receive ondansetron for up to 5 consecutive days of chemotherapy. One hundred ninety patients received ondansetron during chemotherapy treatments that were similar to previous cycles of chemotherapy during which the patients had received standard antiemetics (identical chemotherapy or differing only by addition/deletion of chemotherapy agents of low emetogenicity). Chemotherapy regimens included cisplatin (n = 99; 52%), doxorubicin (without cisplatin, n = 52; 27%), and other drugs (n = 39; 21%). Patient experiences with nausea and vomiting and side effects with ondansetron and with previous standard antiemetics were rated on a scale of 1 to 10 (1, did not experience; 10, as bad as could be). On the nausea and vomiting scale, 74% of patients improved on ondansetron relative to standard antiemetics. Mean nausea and vomiting scales were 3.9 for ondansetron and 7.7 for standard antiemetics (P < .001). On the side effects scale, 62% of patients improved with ondansetron. Mean side effect scores were 1.8 for ondansetron and 4.5 for standard antiemetics (P < .001). One hundred nine patients assessed the effect of nausea and vomiting on their quality of life by means of the Functional Living Index-Emesis. On a 100-point scale (100=best quality of life), quality of life scores were 65.5 for ondansetron and 39.5 for standard antiemetics (P < .01). Functional Living Index-Emesis scores were higher for 76% of patients during ondansetron treatment as compared with previous chemotherapy with standard antiemetic regimens. Twenty-eight patients (15%) were withdrawn from the study because of nausea and vomiting. Forty-four patients (23%) experienced other adverse effects (headache, 17 patients; diarrhea, eight patients; all other events occurred in two or fewer patients). Only six patients were withdrawn due to adverse effects. In conclusion, ondansetron therapy resulted in significantly improved control of nausea and vomiting, fewer side effects, and better quality of life than standard antiemetic therapy in the same patients receiving similar chemotherapy regimens.

Chemotherapy-induced myocardial infarction in a young man with Hodgkin's disease.

A 32-year-old male with stage IIIA nodular sclerosing Hodgkin's disease and no cardiac risk factors presented with chest pain after receiving chemotherapy consisting of multiple drugs, including vinca alkaloids. He completed an uncomplicated anterior wall myocardial infarction. Coronary angiography documented the absence of significant coronary artery disease. Exercise stress testing with gated scan confirmed loss of anterior wall motion and a decreased left ventricular ejection fraction. Vascular toxicity, including, rarely, myocardial infarction, has been reported following antineoplastic regimens containing vinca alkaloids. Hypercoagulable states, cardiac invasion by tumor, and coronary artery spasm are possible etiologies. Of these, coronary artery spasm appears most likely. Management should include discontinuation of the offending drug and supportive care.

Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma.

BACKGROUND: Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children. However, data regarding therapy with this class of compounds, especially in children under age 6 years, is limited. Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index. Few large prospective clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children. OBJECTIVE: We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma. METHODS: Fluticasone propionate powder (50 microg or 100 microg twice daily) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children (4 to 11 years old) with persistent asthma for 12 weeks in a randomized, double-blind, parallel-group, multi-center trial. Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone. RESULTS: Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 (mean increase from baseline of 0.22 to 0.24 L; p < or = 0.023), clinic morning peak expiratory flow (mean increase from baseline of 48 to 55 L/min; p < or = 0.006), patient-measured morning (p < or = 0.001) and evening (p < or = 0.003) peak expiratory flow, and asthma symptom scores (in all but the 50 microg Diskus group; p < or = 0.036), as well as reduced albuterol use (p < or = 0.002) and nighttime awakenings (p < or = 0.019) at endpoint. Efficacy parameters were not significantly different between the two doses with either device. More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group (p < 0.001). Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion. Adverse events were primarily pharmacologic effects of inhaled corticosteroids, and those related to the study drug occurred with low frequency. Patient satisfaction with both the Diskus and Diskhaler devices was high, with a majority of patients (> 80%) rating them favorably. CONCLUSION: This study demonstrated that fluticasone propionate powder, at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler, was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone.

Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma.

BACKGROUND: Flovent Diskus is a powder formulation of the inhaled corticosteroid fluticasone propionate (FP) delivered via a breath-actuated, multidose inhaler. OBJECTIVE: To determine the efficacy and safety of dry powder FP administered once or twice daily (200 microg per day) to children with persistent asthma. METHODS: Twelve-week, randomized, double-blind, placebo-controlled, multicenter trial with a 52-week, open-label extension. Children aged 4 to 11 were required to have pulmonary function 50% to 85% of predicted values. The population was stratified for baseline therapy (inhaled corticosteroid/cromolyn or bronchodilators only). After a 2-week placebo run-in, 242 patients received dry powder FP 200 microg each morning, dry powder FP 100 microg BID, or placebo for 12 weeks; 192 were rerandomized to the QD or BID regimen for an additional 52 weeks of open-label treatment. Primary endpoints were mean changes in FEV1 and morning PEF recorded at clinic visits. RESULTS: Both dry powder FP regimens significantly improved FEV1, evening PEF, and asthma symptoms at the double-blind phase endpoint (P < or = .017 compared with placebo). The BID regimen also significantly improved morning PEF and nighttime awakenings due to asthma (P < or = .005). Among patients previously treated with inhaled corticosteroids/cromolyn, improvements observed with the QD and BID regimens were similar. Patients switched from BID to open-label QD treatment showed additional improvements at week 52 generally comparable to patients who received the BID regimen during both phases. Fluticasone propionate was well tolerated for up to 64 weeks with few reports of drug-related adverse events or morning plasma cortisol abnormalities. CONCLUSIONS: Once daily dosing of dry powder FP 200 microg is an effective and convenient alternative for children whose asthma is controlled with a more frequent dosing regimen of inhaled corticosteroids.