Table 4.
Level 2 evidence of outcomes achieved with aprepitant in the prevention of CINV due to highly emetogenic chemotherapy in double-blind, multicenter, parallel-group RCTs (all P values vs standard therapy without aprepitant unless otherwise stated)
| Chemotherapy regimen | Antiemetic treatment |
Outcome |
Reference | |||
|---|---|---|---|---|---|---|
|
Acute phase |
Delayed phase |
|||||
| Complete response (%)a | Nausea (median VAS scores; 0=none; 100=worst) | Complete response (%)a | Nausea (median VAS scores; 0=none; 100=worst) | |||
| Cis-based ≥70 mg/m2, 1 cycle | Day 1: Gra 10 mcg/kg + Dex 20 mg + Ap 400 mg Day 2–5: Ap 300 mg (n=54) |
77 | 0 | 52 (P<0.001) | 1 (P=0.003) | Navari et al. 1999 |
| Day 1: Gra 10 mcg/kg + Dex 20 mg + Ap 400 mg Day 2–5: Pla (n=54) |
83 | 0 | 43 (P=0.003) | 3 | ||
| Day 1: Gra 10 mcg/kg + Dex 20 mg + Pla Day 2–5: Pla (n=51) |
57 (P=0.004 vs other two groups combined) | 1 | 16 | 10 | ||
| Cis-based ≥70 mg/m2, 1 cycle | Day −1: Pla Day 1: Gra 10 mcg/kg + Dex 20 mg + Pla Day 2–5: Pla (n=90) |
51 | 7.5 | 22 | 7 | Campos et al. 2001 |
| Day −1: Pla Day 1: Gra 10 mcg/kg + Dex 20 mg + Ap 400 mg Day 2–5: Ap 300 mg (n=86) |
75 (P<0.01) | 1 (P<0.05) | 41 (P<0.05) | 2 (P<0.05) | ||
| Day −1: Ap 400 mg Day 1: Dex 20 mg + Ap 400 mg + Pla Day 2–5: Ap 300 mg (n=89) |
44 | 8.5 | 39 (P<0.05) | 3 (P<0.05) | ||
| Day −1: Pla Day 1: Dex 20 mg + Ap 400 mg + Pla Day 2–5: Ap 300 mg (n=86) |
41 | 9.5 | 39 (P<0.05) | 3 | ||
| Cis-based ≥70 mg/m2, 1 cycle | Day 1: L-758,298 100 mg + Dex 20 mg Day 2–5: Ap 300 mg (n=61) |
44 | 11 | 59 (P<0.005) | 5 | Van Belle et al. 2002 |
| Day 1: L-758,298 100 mg + Dex 20 mg Day 2–5: Pla (n=58) |
36 | 46 | 4 | |||
| Day 1: Ond 32 mg + Dex 20 mg Day 2–5: Pla (n=58) |
83 (P<0.001 vs other two groups combined) | 1 (P<0.005 vs other two groups combined) | 38 | 1 | ||
| Cis-based ≥70 mg/m2, 1 cycle | Day 1: Ap 125 mg + Ond 32 mg + Dex 20 mg Day 2–5: Ap 80 mg + Dex 8 mg (n=131) |
83.2 (P<0.05) | NR | 72.7 (P<0.01) | NR | Chawla et al. 2003 |
| Day 1: Ap 40 mg + Ond 32 mg + Dex 20 mg Day 2–5: Ap 25 mg + Dex 8 mg (n=119)b |
75.6 | NR | 63.9 (P<0.01) | NR | ||
| Day 1: Ond 32 mg + Dex 20 mg + Pla Day 2–5: Dex 8 mg + Pla (n=126) |
71.4 | NR | 45.2 | NR | ||
| Cis-based ≥70 mg/m2, 6 cycles | Day 1: Ap 125 mg + Ond 32 mg + Dex 20 mg Day 2–5: Ap 80 mg + Dex 8 mg (n=81)b |
NR | NR | Cycle 1: 64 (P<0.05) Cycle 6 (n=27): 59 (P<0.05) |
NR | de Wit et al. 2003c |
| Day 1: Ond 32 mg + Dex 20 mg + Pla Day 2–5: Dex 8 mg + Pla (n=86) |
NR | NR | Cycle 1: 49 Cycle 6 (n=33): 34 |
NR | ||
| Cis-based ≥70 mg/m2, 1 cycle | Day 1: Ap 125 mg + Ond 32 mg + Dex 12 mg Day 2–3: Ap 80 mg + Dex 8 mg Day 4: Dex 8 mg (n=260) |
89.2 (P<0.001) | 90.6d | 75.4 (P<0.001) | 75.3d | Hesketh et al. 2003 |
| Day 1: Ond 32 mg + Dex 20 mg + Pla Day 2–4: Dex 8 mg bid + Pla (n=261) |
78.1 | 86.5d | 55.8 | 68.5d | ||
| Cis-based ≥70 mg/m2, 1 cycle | Day 1: Ap 125 mg + Ond 32 mg + Dex 12 mg Day 2–3: Ap 80 mg + Dex 8 mg Day 4: Dex 8 mg (n=283) |
82.8 (P<0.001) | NR | 67.7 (P<0.001) | 73d | Poli-Bigelli et al. 2003 |
| Day 1: Ond 32 mg + Dex 20 mg + Pla Day 2–4: Dex 8 mg bid + Pla (n=286) |
68.4 | NR | 46.8 | 65d | ||
| Cis-based ≥70 mg/m2, 6 cycles | Day 1: Ap 125 mg + Ond 32 mg + Dex 12 mg Day 2–3: Ap 80 mg + Dex 8 mg Day 4: Dex 8 mg (n=547) |
Cycle 1: 61e (P<0.001) Cycle 6 (n=89): 59e (P<0.001) |
de Wit et al. 2004f | |||
| Day 1: Ond 32 mg + Dex 20 mg + Pla Day 2–4: Dex 8 mg bid + Pla (n=552) |
Cycle 1: 46e Cycle 6 (n=78): 40e |
|||||
| Cis-based ≥70 mg/m2, +Cyc (87) and/or Dox (74)g | Day 1: Ap 125 mg + Ond 32 mg + Dex 12 mg Day 2–3: Ap 80 mg + Dex 8 mg Day 4: Dex 8 mg (n=520) |
71 (P<0.005) | NR | 67 (P<0.005) | NR | Gralla et al. 2005f |
| Day 1: Ond 32 mg + Dex 20 mg + Pla Day 2–4: Dex 8 mg bid + Pla (n=523) |
49 | NR | 32 | NR | ||
| Cis-based ≥70 mg/m2, 1 cycle | Day 1: Ap 125 mg + Ond 32 mg + Dex 12 mg Day 2–3: Ap 80 mg + Dex 8 mg Day 4: Dex 8 mg (n=547) |
86 (P<0.001) | 91d (P<0.01) | 72 (P<0.001) | 74d (P<0.05) | Warr et al. 2005af |
| Day 1: Ond 32 mg + Dex 20 mg + Pla Day 2–4: Dex 8 mg bid + Pla (n=552) |
73 | 85d | 51 | 67d | ||
| Cis-based ≥70 mg/m2, 1 cycle | Day 1: Ap 125 mg + Ond 32 mg + Dex 12 mg Day 2–3: Ap 80 mg + Dex 8 mg Day 4: Dex 8 mg (n=484 in total) |
87.7 (P=0.005) | NR | 74.1 (P=0.004) | NR | Schmoll et al. 2006 |
| Day 1: Ond 32 mg + Dex 20 mg Day 2–4: Ond 8 mg bid + Dex 8 mg bid |
79.3 | NR | 63.1 | NR | ||
Defined as no vomiting or use of rescue medication;
Patients initially received aprepitant 375 mg on day 1 and 250 mg on days 2–5 but this arm discontinued due to emerging pharmacokinetic data indicating effect on dexamethasone plasma concentrations;
Extension of Chawla et al. 2003;
Percentage of patients reporting no significant nausea (peak VAS <25);
Results presented as “full protection” defined as no vomiting and no significant nausea (i.e. interfering with daily activities);
Pooled analysis of Hesketh et al. 2003 and Poli-Bigelli et al. 2003;
Analysis limited to patients receiving these concomitant drugs. Other patients received etoposide, fluorouracil, gemcitabine, vinorelbine, paclitaxel, and docetaxel.
Ap, aprepitant; bid, twice daily; CINV, chemotherapy-induced nausea and vomiting; Cis, cisplatin; Cyc, cyclophosphamide; Dex, dexamethasone; Dox, doxorubicin; Gra, granisetron; NR, not reported; Ond, ondansetron; Pla, placebo; RCT, randomized controlled trial; VAS, visual analog scale.