Mallika P Patel1,2, Sarah Woodring2, Dina M Randazzo2,3, Henry S Friedman2, Annick Desjardins2,3, Patrick Healy4, James E Herndon4,5, Frances McSherry4, Eric S Lipp2, Elizabeth Miller2, Katherine B Peters2,3, Mary Lou Affronti6,7,8. 1. Department of Pharmacy, Duke University Hospital, Durham, USA. 2. Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. 3. Department of Neurology, Duke University School of Medicine, Durham, NC, USA. 4. Duke Cancer Center Biostatistics, Durham, NC, USA. 5. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA. 6. Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. mary.affronti@duke.edu. 7. Duke Health, Duke University School of Nursing, Durham, NC, 27710, USA. mary.affronti@duke.edu. 8. Duke School of Nursing Faculty, Primary Investigator, Department of Neuro-Surgery, The Preston Robert Tisch Brain Tumor Center, 047 Baker House, Trent Drive, DUMC Box 3624, Durham, NC, 27710, USA. mary.affronti@duke.edu.
Abstract
PURPOSE: CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated. METHODS:One hundred thirty-six glioma patients receiving their first cycle ofadjuvant temozolomide (150-200 mg/m2/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1-5 with aprepitant day 1: 125 mg, days 2-5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2-7), as well as safety and quality of life (QoL). RESULTS: Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity. CONCLUSIONS: Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV's effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.
RCT Entities:
PURPOSE:CINV remains a distressing side effect experienced by gliomapatients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded gliomapatients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for gliomapatients was investigated. METHODS: One hundred thirty-six gliomapatients receiving their first cycle of adjuvant temozolomide (150-200 mg/m2/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1-5 with aprepitant day 1: 125 mg, days 2-5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2-7), as well as safety and quality of life (QoL). RESULTS:Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity. CONCLUSIONS: Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV's effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.
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