Findings from a phase II trial indicate that gefitinib is a well-tolerated and potentially effective treatment for recurrent glioblastoma.
Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor produced by AstraZeneca under the trade name Iressa.The drug was approved last year by the US Food and Drug Administration as a third-line agent for non-small cell lung cancer. Earlier this month, Japanese investigators released a report showing that treatment with the drug increases the sensitivity of oral cancer to radiotherapy (see Reuters Health report January 2, 2004).The current study, reported in the January 1st issue of the Journal of Clinical Oncology, involved 57 patients with a first recurrence of glioblastoma. Gefitinib was started at a dose of 500 mg/day and dose escalations were permitted in patients treated with enzyme-inducing antiepileptic drugs or dexamethasone. No objective tumor responses were seen in the 53 assessable patients, but only 11 patients had measurable disease when gefitinib was started, lead author Dr. Jeremy N. Rich, from Duke University in Durham, North Carolina, and colleagues note.The 6-month event-free survival (EFS) rate was 13%, the researchers state. The median EFS period was 8.1 weeks and the median overall survival period after treatment initiation was 39.4 weeks. The presence of diarrhea was a predictor of improved overall survival, Adverse effects were generally mild, consisting primarily of skin reactions and diarrhea, the investigators found. Only three patients discontinued gefitinib due to related adverse effects. The occurrence of toxic drug effects appeared to be dose related. The presence of diarrhea was identified as predictor of improved overall survival, whereas EGFR expression did not correlate with either overall survival or EFS.”Our results suggest that targeting EGFR activity in glioblastoma by gefitinib may offer benefit,” the researchers state. “Further study of this agent at higher doses is warranted,” they add.(Source: J Clin Oncol 2004;22:133-142: Reuters Health: January 23, 2004: Oncolink)