title: Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).
abstract: To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mg day(-1)) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1-36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2-104+) weeks and PFS-6 was 14.3% (95% CI 4.0-32.7%). The median overall survival was 24.6 weeks (range 4-104+). No grade 3-4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug.
authors.affiliation: 1Department of Medical Oncology, Bellaria Hospital, Bologna, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Franceschi
authors.forename: G
authors.initials: G
authors.lastname: Cavallo
authors.forename: S
authors.initials: S
authors.lastname: Lonardi
authors.forename: E
authors.initials: E
authors.lastname: Magrini
authors.forename: A
authors.initials: A
authors.lastname: Tosoni
authors.forename: D
authors.initials: D
authors.lastname: Grosso
authors.forename: L
authors.initials: L
authors.lastname: Scopece
authors.forename: V
authors.initials: V
authors.lastname: Blatt
authors.forename: B
authors.initials: B
authors.lastname: Urbini
authors.forename: A
authors.initials: A
authors.lastname: Pession
authors.forename: G
authors.initials: G
authors.lastname: Tallini
authors.forename: L
authors.initials: L
authors.lastname: Crinò
authors.forename: A A
authors.initials: AA
authors.lastname: Brandes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009837:Oligodendroglioma / Q000188:drug therapy / Q000556:secondary; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib