Combination of temsirolimus (CCI-779) with chemoradiation in newly diagnosed glioblastoma multiforme (GBM) (NCCTG trial N027D) is associated with increased infectious risks

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Jann N SarkariaJan C Buckner

Abstract

The mammalian target of rapamycin (mTOR) functions within the phosphoinositide 3-kinase/Akt signaling pathway as a critical modulator of cell survival. The mTOR inhibitor temsirolimus (CCI-779) was combined with chemoradiotherapy in glioblastoma multiforme (GBM) patients in a dose-escalation phase I trial. The first 12 patients were treated with CCI-779 combined with radiation/temozolomide and adjuvant temozolomide. A second cohort of 13 patients was treated with concurrent CCI-779/radiation/temozolomide followed by adjuvant temozolomide monotherapy. Concomitant and adjuvant CCI-779 was associated with a high rate (3 of 12 patients) of grade 4/5 infections. By limiting CCI-779 treatment to the radiation/temozolomide phase and using antibiotic prophylaxis, the rate of infections was reduced, although 2 of 13 patients developed exacerbation of pre-existing fungal or viral infections. Dose-limiting toxicities were observed in 2 of 13 patients with this modified schedule. Weekly CCI-779 (50 mg/week) combined with radiation/temozolomide is the recommended phase II dose and schedule. The immune profile of patients in the second cohort was assessed before, during, and after CCI-779 therapy. There was robust suppression of helper and c...Continue Reading

References

Oct 1, 1992·Clinical Immunology and Immunopathology·H LuoJ Wu
Jan 17, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Y B SuPaul B Chapman
Mar 3, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael B AtkinsMatthew L Sherman
Mar 5, 2005·Blood·Manuela BattagliaMaria-Grazia Roncarolo
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Jun 9, 2005·Oncogene·Eric T ShinoharaBo Lu
Jul 7, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Evanthia GalanisUNKNOWN North Central Cancer Treatment Group
Jul 14, 2005·Investigational New Drugs·Susan M ChangUNKNOWN North American Brain Tumor Consortium and the National Cancer Institute
Jul 21, 2005·International Journal of Radiation Oncology, Biology, Physics·Michael A HughesLawrence Kleinberg
Feb 16, 2006·Neurology·A TosoniA A Brandes
Apr 22, 2006·International Journal of Radiation Oncology, Biology, Physics·Sunil KrishnanUNKNOWN North Central Cancer Treatment Group
Dec 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Manuela BattagliaMaria-Grazia Roncarolo
Jun 1, 2007·The New England Journal of Medicine·Gary HudesUNKNOWN Global ARCC Trial
Jul 7, 2007·Cancer Investigation·Abraham B SchwarzbergMatthew H Kulke
Jan 15, 2008·Transplantation·Lu-En WaiSheri M Krams
Aug 5, 2008·Cell Cycle·Ludovica Bruno, Matthias Merkenschlager
Dec 17, 2008·The Journal of Investigative Dermatology·Tobias SinnbergFriedegund Meier
Mar 18, 2009·Immunological Reviews·David A Fruman, Georges Bismuth
Apr 25, 2009·Nature Reviews. Immunology·Angus W ThomsonGiorgio Raimondi

❮ Previous
Next ❯

Citations

Feb 5, 2013·Cancer Chemotherapy and Pharmacology·Howard A Burris
May 4, 2005·Current Neurology and Neuroscience Reports·Santosh KesariPatrick Y Wen
Feb 9, 2006·Current Oncology Reports·Santosh KesariPatrick Y Wen
Apr 30, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Arshawn Sami, Michael Karsy
Feb 11, 2014·Current Oncology Reports·Mohamed Ali Hamza, Mark Gilbert
Sep 16, 2014·Seminars in Radiation Oncology·Jennifer L Clarke
Aug 7, 2012·Expert Opinion on Drug Safety·Ronald M Bukowski
Jan 1, 2014·Clinical Lung Cancer·Saiama N WaqarRamaswamy Govindan
May 7, 2015·Pharmacology & Therapeutics·Constantinos Alifieris, Dimitrios T Trafalis
May 4, 2012·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Selvakumar AnbalaganEster M Hammond
Jul 17, 2012·Hematology/oncology Clinics of North America·Kevin AntonTina Mayer
Mar 27, 2015·Neoplasia : an International Journal for Oncology Research·Hongxiang WangJuxiang Chen
Aug 9, 2015·Critical Reviews in Oncology/hematology·Lei ChangYong Li
Nov 8, 2012·Clinical & Developmental Immunology·Sadhak SenguptaPrakash Sampath
Apr 5, 2016·Cancers·Kevin KelleyRosamaria Ruggieri
May 3, 2015·Neuro-oncology·Michael D PradosJeffrey M Trent
Jun 4, 2013·International Journal of Radiation Oncology, Biology, Physics·Prakash ChinnaiyanMinesh P Mehta
Sep 10, 2013·Cancer Treatment Reviews·Parvin F PeddiSara A Hurvitz
Jul 9, 2013·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Anne Hansen Ree, Donal Hollywood
Aug 29, 2014·Neuro-oncology·Doreen PachowChristian Mawrin
May 14, 2016·Expert Opinion on Investigational Drugs·Verena StaedtkeJohn Laterra
Aug 13, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Zachary S Morris, Paul M Harari
Aug 2, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mei LiuXiu-Wu Bian
Sep 13, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Leo MascarenhasDouglas S Hawkins
Jul 28, 2020·Pharmaceuticals·Angel Escamilla-RamírezCristina Trejo-Solís
May 5, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wolfgang WickMonika E Hegi
May 26, 2021·Clinical Breast Cancer·Jacob S WittBethany M Anderson
Jul 3, 2021·Cells·Don Carlo Ramos BataraSung-Hak Kim

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Related Papers

American Journal of Respiratory and Critical Care Medicine
Dorothy A WhiteR J Motzer
The New England Journal of Medicine
Gary HudesGlobal ARCC Trial
The New England Journal of Medicine
José BaselgaGabriel N Hortobagyi
European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
I DuranM Niroumand
Targeted Oncology
Nicholas A Barber, Apar Kishor Ganti
© 2021 Meta ULC. All rights reserved