se cisplatin, and nausea and vomiting associated with moderately emetogenic chemotherapy.
Highly Emetogenic Chemotherapy
In 2 multicenter, randomized, parallel, double-blind, controlled clinical studies, the aprepitant regimen (see table below) was compared with standard therapy in patients receiving a chemotherapy regimen that included cisplatin >50 mg/m2 (mean cisplatin dose = 80.2 mg/m2). Of the 550 patients who were randomized to receive the aprepitant regimen, 42% were women, 58% men, 59% White, 3% Asian, 5% Black, 12% Hispanic American, and 21% Multi-Racial. The aprepitant-treated patients in these clinical studies ranged from 14 to 84 years of age, with a mean age of 56 years. 170 patients were 65 years or older, with 29 patients being 75 years or older.
Patients (N = 1105) were randomized to either the aprepitant regimen (N = 550) or standard therapy (N = 555). The treatment regimens are defined in the table below.
Treatment Regimens: Highly Emetogenic Chemotherapy Trials Treatment Regimen Day 1 Days 2 to 4
Aprepitant Aprepitant 125 mg PO
Dexamethasone 12 mg PO
Ondansetron 32 mg I.V. Aprepitant 80 mg PO Daily (Days 2 and 3 only)
Dexamethasone 8 mg PO Daily (morning)
Standard Therapy Dexamethasone 20 mg PO
Ondansetron 32 mg I.V. Dexamethasone 8 mg PO Daily (morning)
Dexamethasone 8 mg PO Daily (evening)
Aprepitant placebo and dexamethasone placebo were used to maintain blinding.
During these studies 95% of the patients in the aprepitant group received a concomitant chemotherapeutic agent in addition to protocol-mandated cisplatin. The most common chemotherapeutic agents and the number of aprepitant patients exposed follow: etoposide (106), fluorouracil (100), gemcitabine (89), vinorelbine (82), paclitaxel (52), cyclophosphamide (50), doxorubicin (38), docetaxel (11).
The antiemetic activity of oral aprepitant was eva luated during the acute phase (0 to 24 hours post-cisplatin treatment), the delayed phase (25 to 120 hours post-cisplatin treatment) and overall (0 to 120 hours post-cisplatin treatment) in Cycle 1. Efficacy was based on eva luation of the following endpoints:
Primary endpoint:
complete response (defined as no emetic episodes and no use of rescue therapy)
Other prespecified endpoints:
complete protection (defined as no emetic episodes, no use of rescue therapy, and a maximum nausea visual analogue scale [VAS] score <25 mm on a 0 to 100 mm scale)
no emesis (defined as no emetic episodes regardless of use of rescue therapy)
no nausea (maximum VAS <5 mm on a 0 to 100 mm scale)
no significant nausea (maximum VAS <25 mm on a 0 to 100 mm scale)
A summary of the key study results from each individual study analysis is shown in Table 1 and in Table 2.
Table 1: Percent of Patients Receiving Highly Emetogenic Chemotherapy Responding by Treatment Group and Phase for Study 1 — Cycle 1 ENDPOINTS Aprepitant
Regimen
(N = 260)*
% Standard
Therapy
(N = 261)
% p-Value
N: Number of patients (older than 18 years of age) who received cisplatin, study drug, and had at least one post-treatment efficacy eva luation.
Overall: 0 to 120 hours post-cisplatin treatment.
Acute phase: 0 to 24 hours post-cisplatin treatment.
Delayed phase: 25 to 120 hours post-cisplatin treatment.
Not statistically significant when adjusted for multiple comparisons.
Not statistically significant.
PRIMARY ENDPOINT
Complete Response&nb |
