Phase II Evaluation of Gefitinib in Patients With Newly Diagnosed Grade 4 Astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074

Journal Article · Wed Jun 01 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.01.070· OSTI ID:21491772

Ballman, Karla V; Wenting, Wu; Giannini, Caterina; Krauss, J C; Buckner, Jan C; James, C D; Scheithauer, Bernd W ^[1]; Behrens, Robert J ^[2]; Flynn, Patrick J ^[3]; Schaefer, Paul L ^[4]; Dakhill, Shaker R ^[5]; Jaeckle, Kurt A ^[6]

---

1. Mayo Clinic Rochester, Rochester, MN (United States)
2. Iowa Oncology Research Association CCOP, Des Moines, IA (United States)
3. Metro Minnesota Community Clinical Oncology Program, St. Louis Park, MN (United States)
4. Toledo Community Hospital Oncology Program CCOP, Toledo, OH (United States)
5. Wichita Community Clinical Oncology Program, Wichita, KS (United States)
6. Mayo Clinic Jacksonville, Jacksonville, FL (United States)

Purpose: Amplification of the epidermal growth factor receptor (EGFR) gene represents one of the most frequent gene alterations in glioblastoma (GBM). In the current study, we evaluated gefitinib, a potent EGFR inhibitor, in the treatment of adults with newly diagnosed GBM. Methods and Materials: Ninety-eight patients (96 evaluable) were accrued between May 18, 2001, and August 2, 2002. All were newly diagnosed GBM patients who were clinically and radiographically stable/improved after radiation treatment (enrollment within 5 weeks of radiation completion). No prior chemotherapy was permitted. EGFR amplification/mutation, as assessed by fluorescence in situ hybridization and immunohistochemistry, was not required for treatment with gefitinib but was studied when tissues were available. Gefitinib was administered at 500 mg each day; for patients receiving dexamethasone or enzyme-inducing (CYP3A4) agents, dose was escalated to a maximum of 1,000 mg QD. Treatment cycles were repeated at 4-week intervals with brain magnetic resonance imaging at 8-week intervals. Results: Overall survival (OS; calculated from time of initial surgery) at 1 year (primary end point) with gefitinib was 54.2%, which was not statistically different compared with that of historical control population (48.9%, data from three previous Phase III North Central Cancer Treatment Group studies of newly diagnosed GBM patients). Progression-free survival (PFS) at 1 year post-RT (16.7%) was also not significantly different to that of historical controls (30.3%). Clinical outcome was not affected by EGFR status (amplification or vIII mutation). Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. Of note, the occurrence of drug-related adverse effects, such as loose stools was associated with improved OS. Conclusions: In our evaluation of nearly 100 patients with newly diagnosed GBM, treatment with adjuvant gefitinib post-radiation was not associated with significant improvement in OS or PFS. However, patients who experienced gefitinib-associated adverse effects (rash/diarrhea) did demonstrate improved OS.

• OSTI ID: 21491772
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 80, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2010.01.070; PII: S0360-3016(10)00273-7; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANTINEOPLASTIC DRUGS
BRAIN
DEXAMETHASONE
EPIDERMIS
EVALUATION
FLUORESCENCE
GENES
GLIOMAS
GROWTH FACTORS
IN-SITU HYBRIDIZATION
NMR IMAGING
RADIOTHERAPY
RECEPTORS
ADRENAL HORMONES
ANIMAL TISSUES
BIOTECHNOLOGY
BODY
CENTRAL NERVOUS SYSTEM
CORTICOSTEROIDS
DIAGNOSTIC TECHNIQUES
DISEASES
DRUGS
EMISSION
EPITHELIUM
GENETIC ENGINEERING
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
KETONES
LUMINESCENCE
MEDICINE
MEMBRANE PROTEINS
MITOGENS
NEOPLASMS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NUCLEAR MEDICINE
NUCLEIC ACID HYBRIDIZATION
ORGANIC COMPOUNDS
ORGANS
PHOTON EMISSION
PREGNANES
PROTEINS
RADIOLOGY
SKIN
STEROID HORMONES
STEROIDS
THERAPY