title: A phase II study of the EGFR inhibitor gefitinib in patients with acute myeloid leukemia.
abstract: Novel therapies for the treatment of acute myeloid leukemia are required to overcome disease resistance and to provide potentially less toxic therapies for older adults. Prior clinical trials involving patients with non-small cell lung cancer have demonstrated the safety and biologic activity of the administration of EGFR inhibitors in carefully selected patients. The potential efficacy of this approach in patients with acute myeloid leukemia is unknown. The effects of gefitinib on differentiation induction and cell viability in AML cell lines and primary patient AML cells were previously reported and cell viability was inhibited in a clinically achievable range. To determine if EGFR inhibitors would be therapeutically efficacious in advanced AML, we performed a phase II trial in which 18 patients with a median age of 72 (range, 57-84 years) were treated with gefitinib (750mg orally daily). While there were no unexpected toxicities, no patients experienced an objective response, though one had stable disease lasting 16 months. We conclude that in spite of pre-clinical activity and anecdotal cases of response to EGFR inhibitors, routine use of the EGFR inhibitor gefitinib as a single agent for advanced AML is not appropriate.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: daniel_deangelo@dfci.harvard.edu.
authors: Daniel J
authors: DJ
authors: Deangelo
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: Donna
authors: D
authors: Neuberg
authors: Massachusetts General Hospital, Boston, MA, USA.
authors: Philip C
authors: PC
authors: Amrein
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, and the Division of Hematology/Oncology, Children's Hospital Boston, Boston, MA, USA.
authors: Jacob
authors: J
authors: Berchuck
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: Martha
authors: M
authors: Wadleigh
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: L Andres
authors: LA
authors: Sirulnik
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: Ilene
authors: I
authors: Galinsky
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, and the Division of Hematology/Oncology, Children's Hospital Boston, Boston, MA, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Todd
authors: T
authors: Golub
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, and the Division of Hematology/Oncology, Children's Hospital Boston, Boston, MA, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Kimberly
authors: K
authors: Stegmaier
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: Richard M
authors: RM
authors: Stone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Chemotherapy; EGFR; Gefitinib; Leukemia