Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study

Abstract

PurposeA phase III study adding aprepitant to a 5HTT3 receptor antagonist plus dexamethasone in germ cell tumor (GCT) patients treated with 5 day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single day cisplatin chemotherapy and is approved as a single-dose alternative. This single arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. MethodsGCT patients receiving 5 day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3 antagonist days 1-5 (days 1, 3, 5, if palonosetron) plus dexamethasone 20 mg days 1, 2, and 4 mg po bid days 6, 7, 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate -no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR>27%. Results65 patients were enrolled of whom 54 were eligible for analysis. Median age was 33. 51 patients received BEP (bleomycin, etoposide, cisplatin) chemotherapy. CR was observed in 13 (24.1%) patients (95% Agresti-Coull binomial C.I. 14.5%, 37.1%).

Palonosetron on Days 1 and 5 Versus Granisetron Daily (Days 1-5) in Germ Cell Tumour Therapy

“…Einhorn et al reported that the CR rate for nausea and vomiting was 34.1% in the acute period and 61.0% in the delayed period when Pal was administered every other day in 41 patients with GCT (15). Adra et al also reported that the CR rate was 29.6% in the acute period and 46.3% in the delayed period when Pal was administered every other day in 54 patients with GCT (16). However, there is no report comparing the efficacy between first-and secondgeneration 5-HT 3 receptor antagonists in BEP chemotherapy.…”

Neurokinin receptors and their implications in various autoimmune diseases

“…(2008) 6 L-773,060 Psychiatric disorders NK1R Blockage of NK1R Kramer et al. (1998) L-760,735 7 Fosaprepitat (also known as MK-0517 and L758,298 (FDA approved) NCT017317 Phase 2 Chemotherapy NK1R Inhibit the specific binding of SP to its receptor NK1R in the vomiting center ( Navari, 2008 ) ( Adra et al., 2016 ; Van Laere et al., 2012 ; Weinstein et al., 2016 , 2018 ) NCT009421 Phase 1 Induced nausea and vomiting NCT016979 Phase 2 NCT015949 Phase3 NCT008159 Phase 1 NCT011151 Phase 1 NCT009921 Phase 1 8 MK-0869 NCT009541 Phase 3 Cisplatin NK1R Inhibit the specific binding of SP to its receptor NK1R in the vomiting center, an inhibitor of CYP3A4 ( de Wit et al., 2003 ; Tattersall et al., 2000 ) NCT009921 Phase 1 chemotherapy Hu et al. (2014) NCT000309 Phase 3 NCT000983 Phase 4 9 MK-0869 NCT000407 Phase 3 Major depressive disorder NK1R Inhibit the specific binding of SP to its receptor NK1R ( Keller et al.…”