Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ).
In malignant glioma (MG) patients undergoing radiation therapy (RT) with concomitant temozolomide, chemoradiation-induced nausea and vomiting (cRINV) degrades quality of life (QoL) and reduces treatment adherence, which thereby potentially compromises cancer control.



We conducted a 6-week phase II single-arm trial of PAL, a second-generation 5-HT3RA antiemetic, for cRINV prevention in MG patients receiving radiation therapy (RT; 54-60 Gy) and concomitant daily temozolomide (TMZ; 75 mg/m(2)/dX42d). Each week before radiation, patients received single-dose palonosetron (PAL) 0.25 mg IV (total = 6 doses). With safety/tolerability as the primary endpoint, the study was designed to differentiate between toxicity rates of 25 % (unacceptable) and 10 % (acceptable) toxicity rates. Secondary endpoints included the percentage of patients achieving cRINV complete response (CR: no emesis or rescue antiemetic) and QoL. Patients reported adverse effects in Common Toxicity Criteria for Adverse Events diaries; recorded vomiting, nausea, and rescue medication use in diaries (which were used to assess cRINV-CR); and reported QoL 4 days/week using the Modified Functional Living Index-Emesis (M-FLIE) and Osoba nausea and vomiting/retching modules.



We enrolled 38 patients (mean age 59 years, 55 % female, 95 % white, 68 % used oral corticosteroids, 76 % reported low alcohol use). Four patients (10.5 %) experienced unacceptable treatment-related toxicity, defined as any grade 3, 4, or 5 non-hematologic toxicity. M-FLIE and Osoba scores showed no evidence of treatment impact on QoL. Overall, cRINV-CR rates for 6 weeks ranged from 67-79 %.



Single-dose weekly PAL is a safe and tolerable antiemetic for cRINV prevention in MG patients receiving standard RT and concomitant TMZ.
Department of Neurosurgery, Duke University Health System, Durham, NC, 27710, USA. affro002@mc.duke.edu.|Duke University School of Nursing, Durham, NC, 27710, USA. affro002@mc.duke.edu.|The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Room 047 Baker House, South Hospital, Trent Drive, Durham, NC, 27710, USA. affro002@mc.duke.edu.
Mary Lou
ML
Affronti
Department of Neurosurgery, Duke University Health System, Durham, NC, 27710, USA.|The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Room 047 Baker House, South Hospital, Trent Drive, Durham, NC, 27710, USA.
Sarah
S
Woodring
Department of Radiation Oncology, Duke University Health System, Durham, NC, 27710, USA.
Karen
K
Allen
Department of Radiation Oncology, Duke University Health System, Durham, NC, 27710, USA.
John
J
Kirkpatrick
The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Room 047 Baker House, South Hospital, Trent Drive, Durham, NC, 27710, USA.|Department of Neurology, Duke University Health System, Durham, NC, 27710, USA.
Katherine B
KB
Peters
Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 27710, USA.
James E
JE
Herndon
Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 27710, USA.
Frances
F
McSherry
Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 27710, USA.
Patrick N
PN
Healy
The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Room 047 Baker House, South Hospital, Trent Drive, Durham, NC, 27710, USA.|Department of Neurology, Duke University Health System, Durham, NC, 27710, USA.
Annick
A
Desjardins
Saint Francis Cancer Center, Hartford, CT, 06105, USA.
James J
JJ
Vredenburgh
Department of Neurosurgery, Duke University Health System, Durham, NC, 27710, USA.|The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Room 047 Baker House, South Hospital, Trent Drive, Durham, NC, 27710, USA.|Department of Medicine, Duke University Health System, Durham, NC, 27710, USA.|Department of Pediatrics, Duke University Health System, Durham, NC, 27710, USA.|Department of Pathology, Duke University Health System, Durham, NC, 27710, USA.
Henry S
HS
Friedman
D061605:Administration, Intravenous; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods*; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077924:Palonosetron; D011788:Quality of Life / Q000523:psychology*; D011812:Quinuclidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D000077204:Temozolomide
D000970:Antineoplastic Agents; D007546:Isoquinolines; D011812:Quinuclidines; D000077924:Palonosetron; D003606:Dacarbazine; D000077204:Temozolomide
Antiemetic guidelines; Chemotherapy; Efficacy; Emesis; Evidence-based practice; Gliomas; Nausea; Radiation-induced nausea and vomiting; Safety; Supportive care