Anna R Damato1, Ruth G N Katumba2, Jingqin Luo3,4, Himachandana Atluri2, Grayson R Talcott2, Ashwin Govindan2,5, Emily A Slat6, Katherine N Weilbaecher2, Yu Tao3,4, Jiayi Huang2, Omar H Butt2, George Ansstas2, Tanner M Johanns2, Milan G Chheda2, Erik D Herzog1,7, Joshua B Rubin8,7, Jian L Campian2. 1. Department of Biology, Washington University, St Louis, Missouri, USA. 2. Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA. 3. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA. 4. Siteman Cancer Center Biostatistics Core, Washington University School of Medicine, St. Louis, Missouri, USA. 5. John T. Milliken Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA. 6. Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA. 7. Department of Neuroscience, Washington University School of Medicine, St Louis, Missouri, USA. 8. Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, USA.
Abstract
Background: Gliomas are the most common primary brain tumor in adults. Current treatments involve surgery, radiation, and temozolomide (TMZ) chemotherapy; however, prognosis remains poor and new approaches are required. Circadian medicine aims to maximize treatment efficacy and/or minimize toxicity by timed delivery of medications in accordance with the daily rhythms of the patient. We published a retrospective study showing greater anti-tumor efficacy for the morning, relative to the evening, administration of TMZ in patients with glioblastoma. We conducted this prospective randomized trial to determine the feasibility, and potential clinical impact, of TMZ chronotherapy in patients with gliomas (NCT02781792). Methods: Adult patients with gliomas (WHO grade II-IV) were enrolled prior to initiation of monthly TMZ therapy and were randomized to receive TMZ either in the morning (AM) before 10 am or in the evening (PM) after 8 pm. Pill diaries were recorded to measure compliance and FACT-Br quality of life (QoL) surveys were completed throughout treatment. Study compliance, adverse events (AE), and overall survival were compared between the two arms. Results: A total of 35 evaluable patients, including 21 with GBM, were analyzed (18 AM patients and 17 PM patients). Compliance data demonstrated the feasibility of timed TMZ dosing. There were no significant differences in AEs, QoL, or survival between the arms. Conclusions: Chronotherapy with TMZ is feasible. A larger study is needed to validate the effect of chronotherapy on clinical efficacy.
Background: Gliomas are the most common primary brain tumor in adults. Current treatments involve surgery, radiation, and temozolomide (TMZ) chemotherapy; however, prognosis remains poor and new approaches are required. Circadian medicine aims to maximize treatment efficacy and/or minimize toxicity by timed delivery of medications in accordance with the daily rhythms of the patient. We published a retrospective study showing greater anti-tumor efficacy for the morning, relative to the evening, administration of TMZ in patients with glioblastoma. We conducted this prospective randomized trial to determine the feasibility, and potential clinical impact, of TMZ chronotherapy in patients with gliomas (NCT02781792). Methods: Adult patients with gliomas (WHO grade II-IV) were enrolled prior to initiation of monthly TMZ therapy and were randomized to receive TMZ either in the morning (AM) before 10 am or in the evening (PM) after 8 pm. Pill diaries were recorded to measure compliance and FACT-Br quality of life (QoL) surveys were completed throughout treatment. Study compliance, adverse events (AE), and overall survival were compared between the two arms. Results: A total of 35 evaluable patients, including 21 with GBM, were analyzed (18 AM patients and 17 PM patients). Compliance data demonstrated the feasibility of timed TMZ dosing. There were no significant differences in AEs, QoL, or survival between the arms. Conclusions: Chronotherapy with TMZ is feasible. A larger study is needed to validate the effect of chronotherapy on clinical efficacy.
Authors: Aaron C Tan; David M Ashley; Giselle Y López; Michael Malinzak; Henry S Friedman; Mustafa Khasraw Journal: CA Cancer J Clin Date: 2020-06-01 Impact factor: 508.702
Authors: Ray Zhang; Nicholas F Lahens; Heather I Ballance; Michael E Hughes; John B Hogenesch Journal: Proc Natl Acad Sci U S A Date: 2014-10-27 Impact factor: 11.205
Authors: Zhen Dong; Guoxin Zhang; Meng Qu; Ryan C Gimple; Qiulian Wu; Zhixin Qiu; Briana C Prager; Xiuxing Wang; Leo J Y Kim; Andrew R Morton; Deobrat Dixit; Wenchao Zhou; Haidong Huang; Bin Li; Zhe Zhu; Shideng Bao; Stephen C Mack; Lukas Chavez; Steve A Kay; Jeremy N Rich Journal: Cancer Discov Date: 2019-08-27 Impact factor: 39.397
Authors: F A Lévi; R Zidani; J M Vannetzel; B Perpoint; C Focan; R Faggiuolo; P Chollet; C Garufi; M Itzhaki; L Dogliotti Journal: J Natl Cancer Inst Date: 1994-11-02 Impact factor: 13.506
Authors: C Houillier; X Wang; G Kaloshi; K Mokhtari; R Guillevin; J Laffaire; S Paris; B Boisselier; A Idbaih; F Laigle-Donadey; K Hoang-Xuan; M Sanson; J-Y Delattre Journal: Neurology Date: 2010-10-26 Impact factor: 11.800
Authors: Anna R Damato; Jingqin Luo; Ruth G N Katumba; Grayson R Talcott; Joshua B Rubin; Erik D Herzog; Jian L Campian Journal: Neurooncol Adv Date: 2021-03-02