Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).
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.
Franceschi
E
E
1Department of Medical Oncology, Bellaria Hospital, Bologna, Italy.
Cavallo
G
G
Lonardi
S
S
Magrini
E
E
Tosoni
A
A
Grosso
D
D
Scopece
L
L
Blatt
V
V
Urbini
B
B
Pession
A
A
Tallini
G
G
Crinò
L
L
Brandes
A A
AA
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
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib