A phase I/II trial of Erlotinib in higher risk myelodysplastic syndromes and acute myeloid leukemia after azacitidine failure.

Abstract

Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100mg/day (n=5) or 150mg/day (n=25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III-IV extra hematological toxicities (skin (n=1), and diarrhea (n=3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML.

• Authors: Sylvain Thepot, Simone Boehrer, Valérie Seegers, Thomas Prebet, Odile Beyne-Rauzy, Eric Wattel, Jacques Delaunay, Emmanuel Raffoux, Mathilde Hunault, Eric Jourdan, Fatiha Chermat, Marie Sebert, Guido Kroemer, Pierre Fenaux, Lionel Adès, Groupe Francophone des Myelodysplasies (GFM)
• Journal: Leukemia research (Leuk Res) Vol. 38 Issue 12 Pg. 1430-4 (Dec 2014) ISSN: 1873-5835 [Electronic] England
• PMID: 25449687 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Protein Kinase Inhibitors
• Quinazolines
• Erlotinib Hydrochloride
• EGFR protein, human
• ErbB Receptors
• Azacitidine

Topics

• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage)
• Azacitidine (administration & dosage)
• Bone Marrow
• ErbB Receptors (antagonists & inhibitors)
• Erlotinib Hydrochloride
• Female
• Humans
• Leukemia, Myeloid, Acute (drug therapy, pathology)
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy, pathology)
• Protein Kinase Inhibitors (administration & dosage)
• Quinazolines (administration & dosage)
• Remission Induction