title: 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.affiliation: Hématologie - Maladies du Sang, Centre Hospitalo-Universitaire, Angers, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Thepot
authors.affiliation: Hématologie, Hôpital Avicenne, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris 13, Bobigny, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Boehrer
authors.affiliation: Service d'Informatique Médicale, Centre Hospitalo-Universitaire, Angers France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Seegers
authors.affiliation: Hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.affiliation: Hématologie, Centre Hospitalo-Universitaire Purpan, Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Beyne-Rauzy
authors.affiliation: Hématologie, Centre Hospitalo-Universitaire Lyon Sud, Lyon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Wattel
authors.affiliation: Hématologie, Centre Hospitalo-Universitaire Hôtel Dieu, Nantes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.affiliation: Hématologie Adulte, Hôpital Saint Louis, APHP, Université Paris 7, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.affiliation: Hématologie - Maladies du Sang, Centre Hospitalo-Universitaire, Angers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Hunault
authors.affiliation: Hématologie, Centre Hospitalier Universitaire de Nimes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jourdan
authors.affiliation: Hématologie Séniors, Hôpital Saint Louis, APHP, Université Paris 7, Paris, France.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Chermat
authors.affiliation: Hématologie Séniors, Hôpital Saint Louis, APHP, Université Paris 7, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Sebert
authors.affiliation: Laboratoire Apoptose, Cancer et Immunité, INSERM U1138, Cordeliers Research Center, Université Paris 5, Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Hématologie Séniors, Hôpital Saint Louis, APHP, Université Paris 7, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.affiliation: Hématologie Séniors, Hôpital Saint Louis, APHP, Université Paris 7, Paris, France. Electronic address: lionel.ades@sls.aphp.fr.
authors.forename: Lionel
authors.initials: L
authors.lastname: Adès
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001374:Azacitidine / Q000008:administration & dosage*; D001853:Bone Marrow; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D012074:Remission Induction
chemical_list: D000964:Antimetabolites, Antineoplastic; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D001374:Azacitidine
keywords: Erlotinib; Higher risk; Myelodysplastic syndrome