Abstract
Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic trioxide (ATO) is synergistic with RT based on several mechanisms of action previously identified, however not tested herein. The MTD of ATO, RT and TMZ was determined in a Phase I trial. We now present the combined Phase I/II data. Patients with newly diagnosed malignant gliomas were eligible for treatment. Patients were treated with RT (60 GY), TMZ (75 mg/m2 daily × 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week ×5 weeks, after completing RT they were treated with TMZ 5/28 for up to 12 months. MRIs were performed every 8 weeks. A total of 42 patients were enrolled in both the Phase I and II trials for this study treatment. Of the 42 enrolled patients (24 M and 18 W) the median age was 54 (24-80) and median KPS 90 (60-100). 28 patients had a GBM and 14 had anaplastic glioma (AG). All patients completed RT/TMZ/ATO and went on to maintenance TMZ. Median number of post RT cycles of TMZ was 4 (0-12). Median PFS was 7 m for GBM and 75 m for AG and median OS was 17 m for GBM and NR for AG. Best response was CR in 2, SD in 28, PR in 5 and PD in 7. There were no unexpected adverse events. Grade 3 toxicities likely attributable to ATO included p...Continue Reading
References
Jul 1, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D R MacdonaldJ G Cairncross
Sep 1, 2004·International Journal of Radiation Oncology, Biology, Physics·Shoucheng Ning, Susan J Knox
Mar 28, 2006·International Journal of Radiation Oncology, Biology, Physics·Shoucheng Ning, Susan J Knox
Mar 10, 2009·The Lancet Oncology·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Dec 8, 2009·Cancer Letters·Yunbo ZhenKeiji Kawamoto
May 11, 2010·International Journal of Hematology·Rihab Nasr, Hugues de Thé
Aug 28, 2010·Journal of Hematology & Oncology·Clement YedjouRobert McMurray
Sep 21, 2010·Journal of Neuro-oncology·Aalya FatooJohn A Boockvar
Mar 25, 2011·BMB Reports·Sang Kyun LimLuis F Parada
Aug 10, 2012·Journal of Neuro-oncology·Sean A GrimmJeffrey J Raizer
Nov 1, 2012·Neuro-oncology·Therese A DolecekCarol Kruchko
Feb 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Akio IwanamiPaul S Mischel
Apr 30, 2013·Cell Cycle·Akio IwanamiPaul S Mischel
May 23, 2014·The New England Journal of Medicine·Mark R GilbertMinesh P Mehta
May 27, 2014·The New England Journal of Medicine·Olivier L ChinotTimothy Cloughesy
Jul 6, 2014·Journal of Neuro-oncology·Sani H KizilbashJan C Buckner
Apr 30, 2015·Journal of Neuro-oncology·Lakshmi NayakAndrew B Lassman
Oct 30, 2015·Oncotarget·Wenchao ZhouShideng Bao
Jul 3, 2016·Neuro-oncology·Wolfgang WickUNKNOWN Neurooncology Working Group (NOA) of the German Cancer Society
Citations
Mar 22, 2018·Cell Communication and Signaling : CCS·Gabriela Basile CarballoTania Cristina Leite de Sampaio E Spohr
Jan 25, 2019·Oncology Letters·Guan SunYing Cao
Apr 18, 2018·Oncotarget·Liang-Ting LinYi-Jang Lee
Apr 24, 2020·Scientific Reports·Paulo Henrique Dos Santos KlingerElvis Terci Valera
Sep 29, 2020·Cellular & Molecular Biology Letters·Yi Fang, Zhen Zhang
May 17, 2019·BioMed Research International·Meng-Hang YangWan-Sheng Chen
Jul 28, 2020·Pharmaceuticals·Angel Escamilla-RamírezCristina Trejo-Solís
Sep 10, 2020·Cancers·Md Yousuf AliCorinne E Griguer
Oct 19, 2017·Molecular Cancer Research : MCR·Jonathan B BellLeonidas C Platanias
Jan 28, 2021·Cancers·Alexander OuAmy B Heimberger
Jul 16, 2020·Current Drug Metabolism·Elmira MohtashamiAmir R Afshari
Jul 27, 2021·Medicinal Research Reviews·Marthe SönksenHana Bunzen
Aug 2, 2021·Cellular and Molecular Life Sciences : CMLS·Mariana MedeirosMaría Sol Brassesco