Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC).
OBJECTIVE
Rolapitant is a novel, long-acting neurokinin-1 (NK-1) receptor antagonist. This study evaluated the safety and efficacy of four different doses of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC).


METHODS
This randomized, double-blind, active-controlled, global study was conducted in patients receiving cisplatin-based chemotherapy ≥70 mg/m(2). Patients received a 9, 22.5, 90, or 180 mg oral dose of rolapitant or placebo with ondansetron and dexamethasone on day 1 of chemotherapy. The primary end point was complete response (CR; no emesis and no use of rescue medication) in the overall (0 to 120 h) phase of cycle 1. Other assessments were CR in delayed (24-120 h) and acute (0-24 h) phases, no emesis, no significant nausea, and no nausea.


RESULTS
Four hundred fifty-four patients were randomized. All doses of rolapitant improved CR with the greatest benefit observed with rolapitant 180 mg vs. active control in the overall phase (62.5 and 46.7 %, p = 0.032) and in the acute (87.6 vs. 66.7 %, p = 0.001) and delayed (63.6 vs. 48.9 %, p = 0.045) phases. Rates for no emesis and no significant nausea were significantly (p < 0.05) higher with rolapitant 180 mg vs. active control in the overall, acute, and delayed phases. Treatment-related adverse events were largely considered related to the chemotherapy and included constipation, headache, fatigue, and dizziness which were mostly mild or moderate and were similar across treatment groups.


CONCLUSIONS
All doses of rolapitant were well tolerated and showed greater CR rates than active control. Rolapitant 180 mg demonstrated significant clinical efficacy for preventing CINV in the overall, delayed, and acute phases for patients receiving HEC.
The Medical Oncology Centre of Rosebank, 129 Oxford Road, Corner Northwold, Saxonwold, Johannesburg, South Africa. brapoport@rosebankoncology.co.za.
Bernardo
B
Rapoport
The University of Hong Kong, Pok Fu Lam, Hong Kong.
Daniel
D
Chua
TESARO Inc, Waltham, MA, USA.
Allen
A
Poma
TESARO Inc, Waltham, MA, USA.
Sujata
S
Arora
TESARO Inc, Waltham, MA, USA.
Yan
Y
Wang
Centro Oncologico de Rosario, Santa Fe, Argentina.
Luis Enrique
LE
Fein
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy; D064729:Neurokinin-1 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D017294:Ondansetron / Q000627:therapeutic use; D013141:Spiro Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D055815:Young Adult
D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds; D017294:Ondansetron; D003907:Dexamethasone; C578834:rolapitant; D002945:Cisplatin
Antiemetic; Chemotherapy-induced nausea and vomiting (CINV); NK-1 receptor antagonist; Rolapitant