title: A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.
abstract: To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.
authors.affiliation: IIAIGC Headquarters, Dean of Studies, Burlington, VT, USA. richarderickast@gmail.com
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kast
authors.forename: John A
authors.initials: JA
authors.lastname: Boockvar
authors.forename: Ansgar
authors.initials: A
authors.lastname: Brüning
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Chang
authors.forename: Boris
authors.initials: B
authors.lastname: Cvek
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
authors.forename: Alfonso
authors.initials: A
authors.lastname: Duenas-Gonzalez
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.forename: Daniele
authors.initials: D
authors.lastname: Focosi
authors.forename: Seyed H
authors.initials: SH
authors.lastname: Ghaffari
authors.forename: Georg
authors.initials: G
authors.lastname: Karpel-Massler
authors.forename: Kirsi
authors.initials: K
authors.lastname: Ketola
authors.forename: Alireza
authors.initials: A
authors.lastname: Khoshnevisan
authors.forename: Daniel
authors.initials: D
authors.lastname: Keizman
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magné
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
authors.forename: Kerrie
authors.initials: K
authors.lastname: McDonald
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
authors.forename: Nathan
authors.initials: D
authors.lastname: Sassoon
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Pourgholami
authors.forename: Iacopo
authors.initials: I
authors.lastname: Sardi
authors.forename: Avishay
authors.initials: A
authors.lastname: Sella
authors.forename: Kalkunte S
authors.initials: KS
authors.lastname: Srivenugopal
authors.forename: Marco
authors.initials: M
authors.lastname: Tuccori
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.forename: Christian R
authors.initials: CR
authors.lastname: Wirtz
authors.forename: Marc-Eric
authors.initials: ME
authors.lastname: Halatsch
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077608:Aprepitant; D037621:Artemisinins / Q000008:administration & dosage; D001310:Auranofin / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy*; D002216:Captopril / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004221:Disulfiram / Q000008:administration & dosage; D005909:Glioblastoma / Q000188:drug therapy*; D005942:Gluconates / Q000008:administration & dosage; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage; D009025:Morpholines / Q000008:administration & dosage; D019888:Nelfinavir / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D020280:Sertraline / Q000008:administration & dosage; D013386:Succinates / Q000008:administration & dosage; D000077204:Temozolomide
chemical_list: D037621:Artemisinins; D005942:Gluconates; D009025:Morpholines; D013386:Succinates; D000077608:Aprepitant; D001310:Auranofin; D003606:Dacarbazine; C111789:artesunic acid; D002216:Captopril; D019888:Nelfinavir; D020280:Sertraline; D007654:Ketoconazole; D004221:Disulfiram; D000077204:Temozolomide