title: Cilengitide with metronomic temozolomide, procarbazine, and standard radiotherapy in patients with glioblastoma and unmethylated MGMT gene promoter in ExCentric, an open-label phase II trial.
abstract: Newly diagnosed glioblastoma multiforme with unmethylated MGMT promoter has a poor prognosis, with a median survival of 12 months. This phase II study investigated the efficacy and safety of combining the selective integrin inhibitor cilengitide with a combination of metronomic temozolomide and procarbazine for these patients. Eligible patients (newly diagnosed, histologically confirmed supratentorial glioblastoma with unmethylated MGMT promoter) were entered into this multicentre study. Cilengitide (2000 mg IV twice weekly) was commenced 1 week prior to radiotherapy combined with daily temozolomide (60 mg/m(2)) and procarbazine (50 or 100 mg) and, after 4 weeks' break, followed by six adjuvant cycles of temozolomide (50-60 mg/m(2)) and procarbazine (50 or 100 mg) on days 1-20, every 28 days. Cilengitide was continued for up to 12 months or until disease progression or unacceptable toxicity. The primary endpoint for efficacy was a 12-month overall survival rate of 65 %. Twenty-nine patients completed study treatment. Sixteen patients survived for 12 months or more, an overall survival rate of 55 %. The median overall survival was 14.5 months (95 % CI 11.1-19.6) and the median progression-free survival was 7.4 months (95 % CI 6.1-8). Cilengitide combined with metronomic temozolomide and procarbazine in MGMT-promoter unmethylated glioblastoma did not improve survival compared with historical data and does not warrant further investigation.
authors.affiliation: Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia. mustafa.khasraw@sydney.edu.au.|University of Sydney, Sydney, Australia. mustafa.khasraw@sydney.edu.au.|NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. mustafa.khasraw@sydney.edu.au.|Royal North Shore Hospital, Pacific HWY, St Leonards, NSW, 2065, Australia. mustafa.khasraw@sydney.edu.au.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Khasraw
authors.affiliation: Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia.|University of Sydney, Sydney, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lee
authors.affiliation: Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: McCowatt
authors.affiliation: Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kerestes
authors.affiliation: International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Buyse
authors.affiliation: Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia.|University of Sydney, Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Back
authors.affiliation: International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium.|Flinders Medical Centre and Flinders University, Adelaide, Australia.
authors.forename: Ganessan
authors.initials: G
authors.lastname: Kichenadasse
authors.affiliation: Calvary Mater Newcastle Hospital, Newcastle, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ackland
authors.affiliation: Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia.|University of Sydney, Sydney, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Wheeler
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011344:Procarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D012910:Snake Venoms / Q000009:adverse effects / Q000627:therapeutic use*; D000077204:Temozolomide; D017211:Treatment Failure; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D012910:Snake Venoms; D025521:Tumor Suppressor Proteins; D011344:Procarbazine; C422910:Cilengitide; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Cilengitide; Glioblastoma; Procarbazine; Radiotherapy; Temozolomide