Emend for Multiple-day Emetogenic Chemotherapy

In the studies leading to aprepitant's approval, subjects received only one dose of highly emetogenic chemotherapy. Campos et al studied subjects who received their first course of cisplatin containing chemotherapy that included a cisplatin dose 70mg/m2 and reported that aprepitant in addition to granisetron and dexamethasone increased the number of subjects without acute or delayed emesis (p<0.01). A similar study done by Poli-Bigelli et al indicated that adding aprepitant to a standard antiemetic regimen increased the percentage of subjects without emesis and using rescue therapy during the acute phase (83% to 69%; p < 0.001). Adding aprepitant also increased the percentage of subjects with no emesis or use of rescue medications in the delayed phase (68% vs. 47%, p<0.001). Although these studies demonstrate the benefits of aprepitant for a one day chemotherapy regimen, the benefits of adding aprepitant to current standard antiemetic therapy (dexamethasone plus a serotonin receptor antagonist) in subjects receiving multiple days of moderately-high to highly emetogenic chemotherapy have not been examined within a clinical study. We hypothesize that aprepitant with dexamethasone and a serotonin receptor antagonist from days one to two days after finishing chemotherapy will decrease nausea for subjects receiving chemotherapy regimens that include multiple days of treatment with moderately-high to highly emetogenic chemotherapy.

Inclusion criteria

• Subjects with a life expectancy > 3 months
• Subjects with an ECOG performance score < 3
• Subjects with access to a telephone for follow-up
• Subjects able to swallow tablets and capsules

Exclusion criteria

• Subjects who previously received aprepitant as prophylaxis for chemotherapy induced nausea and vomiting.
• Subjects with an allergy, hypersensitivity, or contraindication to aprepitant, dexamethasone, prochlorperazine or a serotonin receptor antagonist.
• Subject with uncontrolled diabetes or a concurrent illness/condition requiring chronic systemic steroids or pre-existing gastrointestinal pathology.
• Subjects with a history of excessive alcohol consumption.
• Women who are pregnant or lactating.
• Subjects with nausea at baseline or chronically using other antiemetic agent(s).
• Subjects currently receiving another investigational agent.
• Subjects taking a medication that can interact with aprepitant, including the following medications:

• warfarin
• oral contraceptives
• tolbutamide
• phenytoin
• midazolam
• ketoconazole
• rifampin
• paroxetine
• diltiazem
• Subjects with poor hepatic or renal function defined as AST > 3 x ULN, ALT > 3 x ULN, total bilirubin > 3 x ULN, alkaline phosphatase > 3 x ULN or serum creatinine >2 mg/dl measured within three months before starting chemotherapy.

Subjects with hepatic metastases with AST > 5 x ULN, ALT > 5 x ULN, total bilirubin > 5 x ULN, alkaline phosphatase > 5 x ULN.