Publications [#98461] of John H Sampson

Papers Published

1. JN Rich, DA Reardon, T Peery, JM Dowell, JA Quinn, KL Penne, CJ Wikstrand, LB Van Duyn, JE Dancey, RE McLendon, JC Kao, TT Stenzel, BK Ahmed Rasheed, SE Tourt-Uhlig, JE Herndon, JJ Vredenburgh, JH Sampson, AH Friedman, DD Bigner, HS Friedman, Phase II trial of gefitinib in recurrent glioblastoma., Journal of clinical oncology : official journal of the American Society of Clinical Oncology, United States, vol. 22 no. 1 (January, 2004), pp. 133-42, ISSN 0732-183X
   (last updated on 2006/06/06)

   Abstract:
   PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.

   Keywords:
   Adult • Aged • Brain Neoplasms • Disease-Free Survival • Dose-Response Relationship, Drug • Enzyme Inhibitors • Epidermal Growth Factor • Female • Glioblastoma • Humans • Male • Middle Aged • Neoplasm Recurrence, Local • Protein-Tyrosine Kinases • Quinazolines • Treatment Outcome • administration & dosage • adverse effects • antagonists & inhibitors • drug therapy* • pathology • therapeutic use*