title: Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.
abstract: OBJECTIVE
  Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC.
  
  
  METHODS
  Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6.
  
  
  RESULTS
  Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021). Over cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p < 0.001). The incidence of treatment-related adverse events during cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed.
  
  
  CONCLUSIONS
  Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated.
authors: The Medical Oncology Centre of Rosebank, Johannesburg, South Africa. Electronic address: brapoport@rapoport.co.za.
authors: Bernardo
authors: B
authors: Rapoport
authors: The West Clinic, Memphis, TN, USA.
authors: Lee
authors: L
authors: Schwartzberg
authors: William Osler Health Services, Brampton, Ontario, Canada.
authors: Martin
authors: M
authors: Chasen
authors: TESARO, Inc., Waltham, MA, USA.
authors: Dan
authors: D
authors: Powers
authors: TESARO, Inc., Waltham, MA, USA.
authors: Sujata
authors: S
authors: Arora
authors: Indiana University School of Medicine - South Bend, South Bend, IN, USA.
authors: Rudolph
authors: R
authors: Navari
authors: Compass Oncology, US Oncology Research, Tualatin, OR, USA.
authors: Ian
authors: I
authors: Schnadig
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003907:Dexamethasone / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D017829:Granisetron / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D017294:Ondansetron / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D019233:Retreatment; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000932:Antiemetics; D003907:Dexamethasone; D017829:Granisetron; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron; D058831:Serotonin 5-HT3 Receptor Antagonists; D013141:Spiro Compounds; C578834:rolapitant
keywords: Antiemetic; Chemotherapy-induced nausea and vomiting; Multiple cycles; Neurokinin-1 receptor antagonist; Rolapitant; Subsequent cycles