title: A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab.
abstract: OBJECTIVE
  Given that the prognosis of recurrent malignant glioma (MG) remains poor, improving quality of life (QoL) through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL) over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV) prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55%) CINV complete response (CR; no emesis or use of rescue antiemetic) with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg) and dexamethasone (DEX; 10 mg) received in conjunction with biweekly irinotecan-bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy). Secondary end points included delayed CINV CR (days 2-5), overall CINV CR (days 1-5), and QoL, fatigue, and toxicity.
  
  
  METHODS
  A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL-DEX. Validated surveys assessed fatigue and QoL.
  
  
  RESULTS
  A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome of acute CINV CR. Following PAL-DEX dose administrations 1-3, acute CINV CR rates were 62%, 68%, and 70%; delayed CINV CR rates were 62%, 66%, and 70%, and overall CINV CR rates were 47%, 57%, and 62%, respectively. Compared to baseline, there was a clinically meaningful increase in fatigue during acute and overall phases, but not in the delayed phase. There were no grade ≥3 PAL-DEX treatment-related toxicities.
  
  
  CONCLUSIONS
  Data suggest that PAL-DEX is effective in preventing CINV in MG patients, which ultimately maintains the QoL of patients with glioma.
authors.affiliation: The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center; Department of Neurosurgery, Duke University Health System; Duke University School of Nursing.
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Affronti
authors.affiliation: The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center; Department of Neurosurgery, Duke University Health System.
authors.forename: Sarah
authors.initials: S
authors.lastname: Woodring
authors.affiliation: The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center; Department of Neurology.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Peters
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC.
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC.
authors.forename: Frances
authors.initials: F
authors.lastname: McSherry
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Healy
authors.affiliation: The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center; Department of Neurology.
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.affiliation: Saint Francis Cancer Center, Hartford, CT, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.affiliation: The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center; Department of Neurosurgery, Duke University Health System.
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
keywords: antiemetic guidelines; chemotherapy; chemotherapy-induced nausea and vomiting; evidence-based practice; glioma; nausea