Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial.

Background: Oral aprepitant, a neurokinin-1 receptor antagonist, is recommended in combination with other anti-emetic agents for the prevention of nausea and vomiting associated with moderately or highly emetogenic chemotherapy in adults, but its efficacy and safety in paediatric patients are unknown. We did this phase 3 trial to examine the safety and efficacy of such treatment in children.

Methods: In this final analysis of a phase 3, randomised, multicentre, double-blind study, patients aged 6 months to 17 years with a documented malignancy who were scheduled to receive either moderately or highly emetogenic chemotherapy were randomly assigned with an interactive voice response system to an age-based and weight-based blinded regimen of aprepitant (125 mg for ages 12-17 years; 3·0 mg/kg up to 125 mg for ages 6 months to <12 years) plus ondansetron on day 1, followed by aprepitant (80 mg for ages 12-17 years; 2·0 mg/kg up to 80 mg for ages 6 months to <12 years) on days 2 and 3, or placebo plus ondansetron on day 1 followed by placebo on days 2 and 3; addition of dexamethasone was allowed.

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE.

Purpose: Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours).

A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia.

Background: Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients.

Methods: Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or L-AmB (3 mg/kg daily) in a 2:1 ratio.

Caspofungin use in patients with invasive candidiasis caused by common non-albicans Candida species: review of the caspofungin database.

Increasing rates of invasive candidiasis caused by non-albicans Candida species have been reported worldwide. Particular concerns have been raised for C. parapsilosis because of reduced in vitro susceptibility to echinocandins.

Safety experience with caspofungin in pediatric patients.

We analyzed the caspofungin safety experience in 5 clinical registration studies in 171 pediatric patients, 1 week to 17 years of age. Caspofungin was administered for 1 to 87 (mean 12.1) days.

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study.

Purpose: Aprepitant was shown previously to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) in breast cancer patients receiving an anthracycline and cyclophosphamide (AC)-based regimen. This study assessed aprepitant in patients receiving a broad range of MEC regimens with a variety of tumor types.

Methods: This phase III, randomized, gender-stratified, double-blind trial enrolled patients with confirmed malignancies, naïve to MEC or highly emetogenic chemotherapy, who were scheduled to receive a single dose of at least one MEC agent.

A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis.

Background: The standard caspofungin treatment regimen (50 mg/day after a 70-mg dose on day 1) is effective and well tolerated for the treatment of invasive candidiasis, but experience with higher doses of caspofungin is limited. We evaluated the safety and efficacy of caspofungin at 3 times the standard dosing regimen.

Methods: Patients with proven invasive candidiasis were randomized to receive a standard or high-dose (150 mg/day) caspofungin treatment regimen.

A prospective, multicenter study of caspofungin for the treatment of documented Candida or Aspergillus infections in pediatric patients.

Objective: We evaluated the safety, tolerability, and efficacy of caspofungin in pediatric patients with invasive aspergillosis, invasive candidiasis, or esophageal candidiasis.

Methods: This was a multicenter, prospective, open-label study in children 3 months to 17 years of age with proven or probable invasive aspergillosis, proven invasive candidiasis, or proven esophageal candidiasis. All of the patients received caspofungin 70 mg/m(2) on day 1, followed by 50 mg/m(2) per day (maximum: 70 mg/day), as primary or salvage monotherapy.

Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability.

Background: The neurokinin-1 receptor antagonist aprepitant, plus a 5HT3 antagonist and corticosteroid is well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in adults but has not been formally assessed in adolescents.

Procedure: Patients age 11-19 years old receiving emetogenic chemotherapy were randomized 2:1 to aprepitant triple therapy (aprepitant [A] 125 mg p.o.

Caspofungin for the treatment of less common forms of invasive candidiasis.

Objectives: Caspofungin has demonstrated efficacy in invasive candidiasis. However, in a comparative study, most patients (>83%) had candidaemia. Therefore, we performed a study in patients with non-fungaemic invasive candidiasis.

Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis.

Background: Caspofungin inhibits synthesis of beta-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA.

Efficacy of caspofungin against invasive Candida or invasive Aspergillus infections in neutropenic patients.

Background: Neutropenia is an indicator of poor prognosis in patients with fungal infections. All available clinical trial experience from the caspofungin development program was reviewed to ascertain the efficacy of caspofungin in neutropenic patients with documented invasive aspergillosis (IA) or invasive candidiasis (IC).

Methods: The review was limited to neutropenic patients with proven IC or proven/probable IA at caspofungin onset.

The oral NK(1) antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: Pooled data from 2 randomised, double-blind, placebo controlled trials.

In this work, data from two phase III studies were pooled to further evaluate the NK(1) antagonist aprepitant for prevention of cisplatin induced nausea and vomiting. One thousand and forty three patients receiving cisplatin (> or = 70 mg/m2) were randomised to receive either a control regimen (32 mg intravenous ondansetron [O] and 20 mg oral dexamethasone [D] on day 1; 8 mg D twice daily on days 2-4) or an aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2-3, and 8 mg D on day 4). The primary endpoint was no emesis and no rescue therapy.

Evaluation of serum sandwich enzyme-linked immunosorbent assay for circulating galactomannan during caspofungin therapy: results from the caspofungin invasive aspergillosis study.

There has been minimal clinical experience with the use of the Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) for patients receiving echinocandin therapy. We reviewed the experience with the galactomannan ELISA for 17 patients in a study of caspofungin treatment for invasive aspergillosis. The rate of successful outcomes for these patients was similar to that overall for participants in the study.

Salvage therapy with caspofungin for invasive aspergillosis: results from the caspofungin compassionate use study.

Objectives: The objective was to prospectively assess the efficacy and safety of caspofungin as salvage therapy for invasive aspergillosis in patients enrolled in the caspofungin compassionate-use study.

Methods: Forty-eight patients with invasive Aspergillus infections (36 with pulmonary infection, 12 with extrapulmonary or disseminated infection) were enrolled in this study. All patients were refractory to or intolerant of intravenous amphotericin B or a lipid amphotericin formulation(s).

Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.

Background: Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species.

Methods: We investigated the efficacy and safety of caspofungin in the treatment of IA.

Second-line therapy with caspofungin for mucosal or invasive candidiasis: results from the caspofungin compassionate-use study.

Objectives: To prospectively assess the efficacy and safety of caspofungin as second-line therapy for mucosal or invasive candidiasis in patients enrolled in the caspofungin compassionate-use study.

Materials And Methods: Thirty-seven patients with mucosal or invasive candida infections (17 oesophageal, four oropharyngeal and 16 invasive candidiasis) were enrolled in the caspofungin compassionate-use study. All patients were refractory to or intolerant of intravenous amphotericin B or lipid amphotericin formulation(s).

Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting.

Background: The neurokinin-1 antagonist aprepitant (EMEND; Merck Research Laboratories, West Point, PA) has been shown to reduce chemotherapy-induced nausea and vomiting when it is given with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. The current study sought to define the most appropriate dose regimen of oral aprepitant.

Methods: This multicenter, randomized, double-blind, placebo-controlled study was conducted in patients with cancer who were receiving initial cisplatin (> or = 70 mg/m(2)) and standard antiemetic therapy (intravenous ondansetron plus oral dexamethasone).