Thema: News: ZD1839 for patients with first relapse glioblastoma
News: ZD1839 for patients with first relapse glioblastoma
Tom[a]
19.07.2003 22:24:00
39th ASCO Annual Meeting . Chicago, IL . May 31-June 3, 2003 (Abstract No. 396)
Phase II trial of ZD1839 for patients with first relapse glioblastoma
T. S. Peery, D. A. Reardon, J. Quinn, J. Ochs, C. Wikstrand, T. T. Stenzel, D. D. Bigner, H. S. Friedman, J. N. Rich, J. Dancey
Duke University Medical Center, Durham, NC; Astra Zeneca, Wayne, PA; National Cancer Institute, Bethesda, MD
The epidermal growth factor receptor (EGFR) pathway is dysregulated in the majority of glioblastomas. ZD1839 is a potent in vitro inhibitor of EGFR tyrosine kinase that has significant activity in a subset of systemic cancers in clinical trials.
We are conducting a phase II trial to evaluate the activity of ZD1839 in the treatment of adults with first relapse glioblastoma and to correlate response with tumor EGFR status. Patients with histologically confirmed glioblastoma are dosed at 500 mg daily with patients receiving dexamethasone and/or enzyme-inducing (CYP3A4) agents escalated to a dose of 1000 mg.
Treatment cycles are repeated at 4-week intervals with tumor response assessed by brain MRI at 8-week intervals.
To date, fifty-seven pts have been treated. Of 52 evaluable pts, one (2%) has maintained a partial response through 9 cycles, 22 (42%) achieved stable disease (SD), and 29 (56%) had progressive disease (PD). Of the patients with SD, 8 remain on therapy with a mean follow-up of 5.3 months (range: 2-10) and 9 have progressed (mean time to progression 4.4 months, range: 2-6).
Five patients with radiographically stable disease were removed from the trial due to toxicity (n = 2) or clinical decline (n = 3). Eight pts (15%) have been treated for greater than 5 months. Significant toxicity (Grade 3-4; >1 event) was limited to rash (n = 4) and diarrhea (n = 6).
Immunohistochemistry (ICH) of tumors revealed that 39 of 48 pts (81%) expressed wild-type (wt) EGFR while a constitutively active mutant EGFR (EGFRvIII) was present in 20 of 47 (43%) pts.
To date, semiquantitative PCR analysis revealed amplification of wild-type EGFR DNA in 6 of 14 pts (43%), including 2 cases (33%) that also expressed EGFRvIII by ICH. We are currently correlating EGFR expression with clinical response to ZD1839. In conclusion, ZD1839 is well tolerated and has modest activity in patients with recurrent glioblastoma.
© Copyright 2003 American Society of Clinical Oncology All rights reserved worldwide
Phase II trial of ZD1839 for patients with first relapse glioblastoma
T. S. Peery, D. A. Reardon, J. Quinn, J. Ochs, C. Wikstrand, T. T. Stenzel, D. D. Bigner, H. S. Friedman, J. N. Rich, J. Dancey
Duke University Medical Center, Durham, NC; Astra Zeneca, Wayne, PA; National Cancer Institute, Bethesda, MD
The epidermal growth factor receptor (EGFR) pathway is dysregulated in the majority of glioblastomas. ZD1839 is a potent in vitro inhibitor of EGFR tyrosine kinase that has significant activity in a subset of systemic cancers in clinical trials.
We are conducting a phase II trial to evaluate the activity of ZD1839 in the treatment of adults with first relapse glioblastoma and to correlate response with tumor EGFR status. Patients with histologically confirmed glioblastoma are dosed at 500 mg daily with patients receiving dexamethasone and/or enzyme-inducing (CYP3A4) agents escalated to a dose of 1000 mg.
Treatment cycles are repeated at 4-week intervals with tumor response assessed by brain MRI at 8-week intervals.
To date, fifty-seven pts have been treated. Of 52 evaluable pts, one (2%) has maintained a partial response through 9 cycles, 22 (42%) achieved stable disease (SD), and 29 (56%) had progressive disease (PD). Of the patients with SD, 8 remain on therapy with a mean follow-up of 5.3 months (range: 2-10) and 9 have progressed (mean time to progression 4.4 months, range: 2-6).
Five patients with radiographically stable disease were removed from the trial due to toxicity (n = 2) or clinical decline (n = 3). Eight pts (15%) have been treated for greater than 5 months. Significant toxicity (Grade 3-4; >1 event) was limited to rash (n = 4) and diarrhea (n = 6).
Immunohistochemistry (ICH) of tumors revealed that 39 of 48 pts (81%) expressed wild-type (wt) EGFR while a constitutively active mutant EGFR (EGFRvIII) was present in 20 of 47 (43%) pts.
To date, semiquantitative PCR analysis revealed amplification of wild-type EGFR DNA in 6 of 14 pts (43%), including 2 cases (33%) that also expressed EGFRvIII by ICH. We are currently correlating EGFR expression with clinical response to ZD1839. In conclusion, ZD1839 is well tolerated and has modest activity in patients with recurrent glioblastoma.
© Copyright 2003 American Society of Clinical Oncology All rights reserved worldwide
Tom[a]
