title: Phase II trial of ritonavir/lopinavir in patients with progressive or recurrent high-grade gliomas.
abstract: Current therapies for recurrent or progressive high-grade gliomas (HGG, WHO grade 3-4) produce a 6-month progression-free survival of only 10-25%. Migration and invasion by HGG is mediated in part by matrix metalloproteases (MMPs) which promote remodeling of the extracellular matrix. Several HIV protease inhibitors (HIVPI) decrease the expression of MMPs in astrocytes and microglia. Given these mechanisms of antitumor activity of HIVPI, we evaluated the efficacy of ritonavir/lopinavir, a combination HIVPI, in patients with progressive or recurrent HGG in an open label phase II trial. Nineteen patients were treated in this study. Patients received ritonavir/lopinavir (400 mg/100 mg) orally twice daily. All patients were treated until progression of disease or unacceptable toxicity. A complete response was seen in one patient (5%). Three patients (16%) had stable disease as the best response. Fifteen patients (79%) had progressive disease. The 6-month progression free survival (PFS(6)) was 11% (2 of 19 patients). Ritonavir/lopinavir was well tolerated in patients with heavily pretreated refractory HGG, and no grade 3 or 4 toxicity was seen. The activity at the dose and schedule used in this study, however, was modest and the study did not meet its efficacy endpoint.
authors.affiliation: Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, R35, Cleveland, OH 44195, USA.
authors.forename: Manmeet S
authors.initials: MS
authors.lastname: Ahluwalia
authors.forename: Carol
authors.initials: C
authors.lastname: Patton
authors.forename: Glen
authors.initials: G
authors.lastname: Stevens
authors.forename: Tanya
authors.initials: T
authors.lastname: Tekautz
authors.forename: Lilyana
authors.initials: L
authors.lastname: Angelov
authors.forename: Michael A
authors.initials: MA
authors.lastname: Vogelbaum
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weil
authors.forename: Sam
authors.initials: S
authors.lastname: Chao
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: John H
authors.initials: JH
authors.lastname: Suh
authors.forename: Gene H
authors.initials: GH
authors.lastname: Barnett
authors.forename: David M
authors.initials: DM
authors.lastname: Peereboom
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011744:Pyrimidinones / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir