title: Preclinical impact of bevacizumab on brain and tumor distribution of irinotecan and temozolomide.
abstract: Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Prognosis of GBM patients is poor with median overall survival around 15 months. Temozolomide is the chemotherapeutic agent used in the standard of care of newly diagnosed GBM patients relying on radiotherapy with concurrent chemotherapy followed by chemotherapy alone. Irinotecan has shown some efficacy in recurrent malignant gliomas. Bevacizumab has been combined with irinotecan in the treatment of recurrent GBM and with temozolomide in newly diagnosed GBM. As the efficacy of GBM treatments relies on their brain distribution through the blood brain barrier, the aim of the present preclinical work was to study, in in vivo models, the impact of bevacizumab on brain and tumor distribution of temozolomide and irinotecan. Our results show that bevacizumab pre-treatment was associated with a reduced temozolomide brain distribution in tumor-free mice. In tumor bearing mice, bevacizumab increased temozolomide tumor distribution, although not statistically significant. In both tumor-free and tumor-bearing mice, bevacizumab does not modify brain distribution of irinotecan and its metabolite SN-38. Bevacizumab impacts brain distribution of some anti-tumor drugs and potentially their efficacy in GBM. Further studies are warranted to investigate other therapeutic combination.
authors: Clinical Pharmacy Department - EA 4123, College of Pharmacy, Paris Sud University, 5 rue Jean Baptiste Clement, 92296, Châtenay Malabry, France, lauriane.goldwirt@sls.aphp.fr.
authors: Lauriane
authors: L
authors: Goldwirt
authors: Kevin
authors: K
authors: Beccaria
authors: Alexandre
authors: A
authors: Carpentier
authors: Ahmed
authors: A
authors: Idbaih
authors: Charlotte
authors: C
authors: Schmitt
authors: Camille
authors: C
authors: Levasseur
authors: Marianne
authors: M
authors: Labussiere
authors: Aline
authors: A
authors: Milane
authors: Robert
authors: R
authors: Farinotti
authors: Christine
authors: C
authors: Fernandez
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D000068258:Bevacizumab / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000077204:Temozolomide; D014018:Tissue Distribution
chemical_list: D020533:Angiogenesis Inhibitors; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D000068258:Bevacizumab; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide