Phase I trial of erlotinib with radiation therapy in patients with glioblastoma multiforme: Results of north central cancer treatment group protocol N0177

被引:67
作者
Krishnan, Sunil
Brown, Paul D.
Ballman, Karla V.
Fiveash, John B.
Uhm, Joon H.
Giannini, Caterina
Jaeckle, Kurt A.
Geoffroy, Francois J.
Nabors, L. Burt
Buckner, Jan C.
机构
[1] Mayo Clin & Mayo Fdn, Coll Med, Dept Radiat Oncol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Coll Med, Div Biostat, Rochester, MN 55905 USA
[3] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA
[4] Mayo Clin & Mayo Fdn, Coll Med, Dept Neurol, Rochester, MN 55905 USA
[5] Mayo Clin & Mayo Fdn, Coll Med, Dept Pathol, Rochester, MN 55905 USA
[6] Mayo Clin & Mayo Fdn, Coll Med, Dept Neurol, Rochester, MN 55905 USA
[7] Mayo Clin & Mayo Fdn, Coll Med, Dept Oncol, Rochester, MN 55905 USA
[8] Oncol Hematol Assoc Cent Illinois, Peoria, IL USA
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2006年 / 65卷 / 04期
关键词
erlotonib; radiation therapy; glioblastoma multiforme;
D O I
10.1016/j.ijrobp.2006.01.018
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib plus radiation therapy (RT) in patients with glioblastoma multiforme (GBM) in a multicenter phase I trial. Methods and Materials: Patients were stratified on the basis of the use of enzyme-inducing anticonvulsants (EIACs). After resection or biopsy, patients were treated with erlotinib for 1 week before concurrent erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until progression. The erlotinib dose was escalated in cohorts of 3 starting at 100 mg/day. Results: Twenty patients were enrolled and 19 were evaluable for the MTD and efficacy endpoints. Of these patients, 14 were males and 5 were females, with a median age of 54 years. Seven had undergone biopsy only, 5 had subtotal resections, and 7 had gross total resections. The highest dose level was 150 mg/day erlotinib for patients not on EIACs (Group 1) and 200 mg/day for patients on EIACs (Group 2). MTD was not reached in either group. In Group 1 at 100 mg (n = 6) and at 150 mg (n = 4), only 1 dose-limiting toxicity (DLT) occurred (stomatitis at 100 mg). No DLTs have occurred in Group 2 at 100 mg (n = 3), 150 mg (n = 3), and 200 mg (n = 3). With a median follow-up of 52 weeks, progression was documented in 16 patients and 13 deaths occurred. Median time to progression was 26 weeks, and median survival was 55 weeks. Conclusion: Toxicity is acceptable at the current doses of erlotinib plus RT. The study was modified to include concurrm-tand adjuvant temozolomide, and accrual is in progress. (c) 2006 Elsevier Inc.
引用
收藏
页码:1192 / 1199
页数:8
相关论文
共 48 条
  • [1] Afra D, 2002, LANCET, V359, P1011
  • [2] The importance of genomic copy number changes in the prognosis of glioblastoma multiforme
    Arslantas, A
    Artan, S
    Öner, Ü
    Müslümanoglu, H
    Durmaz, R
    Cosan, E
    Atasoy, MA
    Basaran, N
    Tel, E
    [J]. NEUROSURGICAL REVIEW, 2004, 27 (01) : 58 - 64
  • [3] EGFR overexpression and radiation response in glioblastoma multiforme
    Barker, FG
    Simmons, ML
    Chang, SM
    Prados, MD
    Larson, DA
    Sneed, PK
    Wara, WM
    Berger, MS
    Chen, PC
    Israel, MA
    Aldape, KD
    [J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2001, 51 (02): : 410 - 418
  • [4] Proliferation and motility responses of primary and recurrent gliomas related to changes in epidermal growth factor receptor expression
    Berens, ME
    Rief, MD
    Shapiro, JR
    Haskett, D
    Giese, A
    Joy, A
    Coons, SW
    [J]. JOURNAL OF NEURO-ONCOLOGY, 1996, 27 (01) : 11 - 22
  • [5] Bouvier-Labit C, 1998, NEUROPATH APPL NEURO, V24, P381
  • [6] Immunohistochemically determined total epidermal growth factor receptor levels not of prognostic value in newly diagnosed glioblastoma multiforme: Report from the Radiation Therapy Oncology Group
    Chakravarti, A
    Seiferheld, W
    Tu, XY
    Wang, HJ
    Zhang, HZ
    Ang, KK
    Hammond, E
    Curran, W
    Mehta, M
    [J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2005, 62 (02): : 318 - 327
  • [7] Medical progress: Brain tumors
    DeAngelis, LM
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (02) : 114 - 123
  • [8] Radiation-induced release of transforming growth factor α activates the epidermal growth factor receptor and mitogen-activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation-induced cell death
    Dent, P
    Reardon, DB
    Park, JS
    Bowers, G
    Logsdon, C
    Valerie, K
    Schmidt-Ullrich, R
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (08) : 2493 - 2506
  • [9] Etienne MC, 1998, CLIN CANCER RES, V4, P2383
  • [10] Signal transduction pathways and their relevance in human astrocytomas
    Feldkamp, MM
    Lau, N
    Guha, A
    [J]. JOURNAL OF NEURO-ONCOLOGY, 1997, 35 (03) : 223 - 248