A Pilot Phase II Study of Erlotinib for the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia

Iman Abou Dalle, Jorge E. Cortes, Pramod Pinnamaneni, Betty Lamothe, Adolfo Diaz Duque, Jasleen Randhawa, Naveen Pemmaraju, Elias Jabbour, Alessandra Ferrajoli, William G. Wierda, Zeev Estrov, Marina Konopleva, Farhad Ravandi, Yesid Alvarado, Gautam Borthakur, Varsha Gandhi, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

Erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, may have off-target activity inducing acute myeloid leukemia (AML) differentiation, possibly through SYK inhibition. We investigated erlotinib in a pilot phase II study for efficacy in relapsed/refractory AML patients at a dose of 150 mg once daily in 28-day cycles. Twenty-nine patients were treated for a median of 29 days (range 12-142 days). Seven patients (24%) received > 1 cycle of therapy and 12 (41%) discontinued treatment before day 28 due to disease progression. One patient (3%) achieved complete remission and 2 (7%) a > 50% reduction in blasts. The most common toxicities associated with erlotinib were fatigue in 10 patients (34%), diarrhea in 10 (34%), nausea in 8 (28%), and rash in 7 (24%). Only 2 patients (7%) had study drug-related adverse events requiring dose reductions and eventual discontinuation. The main reason for treatment discontinuation was disease progression in 26 patients (90%). All patients had died by the time of the last follow-up. Progression of disease was the primary cause of death in all patients. Median overall survival was 14 weeks (range 2.3-96.9 weeks) and median event-free survival was 5 weeks (range 1.7-21.0 weeks). Erlotinib as a single agent has limited clinical efficacy in patients with relapsed/refractory AML.

Original languageEnglish (US)
Pages (from-to)30-39
Number of pages10
JournalActa Haematologica
Volume140
Issue number1
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

Fingerprint

Acute Myeloid Leukemia
Therapeutics
Disease Progression
Erlotinib Hydrochloride
Exanthema
Drug-Related Side Effects and Adverse Reactions
Epidermal Growth Factor Receptor
Nausea
Disease-Free Survival
Fatigue
Cause of Death
Diarrhea
Survival

Keywords

  • Acute myeloid leukemia
  • Erlotinib
  • Relapsed/refractory AML

ASJC Scopus subject areas

  • Hematology

Cite this

Dalle, I. A., Cortes, J. E., Pinnamaneni, P., Lamothe, B., Duque, A. D., Randhawa, J., ... Kantarjian, H. M. (2018). A Pilot Phase II Study of Erlotinib for the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia. Acta Haematologica, 140(1), 30-39. https://doi.org/10.1159/000490092

A Pilot Phase II Study of Erlotinib for the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia. / Dalle, Iman Abou; Cortes, Jorge E.; Pinnamaneni, Pramod; Lamothe, Betty; Duque, Adolfo Diaz; Randhawa, Jasleen; Pemmaraju, Naveen; Jabbour, Elias; Ferrajoli, Alessandra; Wierda, William G.; Estrov, Zeev; Konopleva, Marina; Ravandi, Farhad; Alvarado, Yesid; Borthakur, Gautam; Gandhi, Varsha; Kantarjian, Hagop M.

In: Acta Haematologica, Vol. 140, No. 1, 01.09.2018, p. 30-39.

Research output: Contribution to journalArticle

Dalle, IA, Cortes, JE, Pinnamaneni, P, Lamothe, B, Duque, AD, Randhawa, J, Pemmaraju, N, Jabbour, E, Ferrajoli, A, Wierda, WG, Estrov, Z, Konopleva, M, Ravandi, F, Alvarado, Y, Borthakur, G, Gandhi, V & Kantarjian, HM 2018, 'A Pilot Phase II Study of Erlotinib for the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia', Acta Haematologica, vol. 140, no. 1, pp. 30-39. https://doi.org/10.1159/000490092
Dalle, Iman Abou ; Cortes, Jorge E. ; Pinnamaneni, Pramod ; Lamothe, Betty ; Duque, Adolfo Diaz ; Randhawa, Jasleen ; Pemmaraju, Naveen ; Jabbour, Elias ; Ferrajoli, Alessandra ; Wierda, William G. ; Estrov, Zeev ; Konopleva, Marina ; Ravandi, Farhad ; Alvarado, Yesid ; Borthakur, Gautam ; Gandhi, Varsha ; Kantarjian, Hagop M. / A Pilot Phase II Study of Erlotinib for the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia. In: Acta Haematologica. 2018 ; Vol. 140, No. 1. pp. 30-39.
@article{5ea42c71519b4936a13fa969e115bc58,
title = "A Pilot Phase II Study of Erlotinib for the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia",
abstract = "Erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, may have off-target activity inducing acute myeloid leukemia (AML) differentiation, possibly through SYK inhibition. We investigated erlotinib in a pilot phase II study for efficacy in relapsed/refractory AML patients at a dose of 150 mg once daily in 28-day cycles. Twenty-nine patients were treated for a median of 29 days (range 12-142 days). Seven patients (24{\%}) received > 1 cycle of therapy and 12 (41{\%}) discontinued treatment before day 28 due to disease progression. One patient (3{\%}) achieved complete remission and 2 (7{\%}) a > 50{\%} reduction in blasts. The most common toxicities associated with erlotinib were fatigue in 10 patients (34{\%}), diarrhea in 10 (34{\%}), nausea in 8 (28{\%}), and rash in 7 (24{\%}). Only 2 patients (7{\%}) had study drug-related adverse events requiring dose reductions and eventual discontinuation. The main reason for treatment discontinuation was disease progression in 26 patients (90{\%}). All patients had died by the time of the last follow-up. Progression of disease was the primary cause of death in all patients. Median overall survival was 14 weeks (range 2.3-96.9 weeks) and median event-free survival was 5 weeks (range 1.7-21.0 weeks). Erlotinib as a single agent has limited clinical efficacy in patients with relapsed/refractory AML.",
keywords = "Acute myeloid leukemia, Erlotinib, Relapsed/refractory AML",
author = "Dalle, {Iman Abou} and Cortes, {Jorge E.} and Pramod Pinnamaneni and Betty Lamothe and Duque, {Adolfo Diaz} and Jasleen Randhawa and Naveen Pemmaraju and Elias Jabbour and Alessandra Ferrajoli and Wierda, {William G.} and Zeev Estrov and Marina Konopleva and Farhad Ravandi and Yesid Alvarado and Gautam Borthakur and Varsha Gandhi and Kantarjian, {Hagop M.}",
year = "2018",
month = "9",
day = "1",
doi = "10.1159/000490092",
language = "English (US)",
volume = "140",
pages = "30--39",
journal = "Acta Haematologica",
issn = "0001-5792",
publisher = "S. Karger AG",
number = "1",

}

TY - JOUR

T1 - A Pilot Phase II Study of Erlotinib for the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia

AU - Dalle, Iman Abou

AU - Cortes, Jorge E.

AU - Pinnamaneni, Pramod

AU - Lamothe, Betty

AU - Duque, Adolfo Diaz

AU - Randhawa, Jasleen

AU - Pemmaraju, Naveen

AU - Jabbour, Elias

AU - Ferrajoli, Alessandra

AU - Wierda, William G.

AU - Estrov, Zeev

AU - Konopleva, Marina

AU - Ravandi, Farhad

AU - Alvarado, Yesid

AU - Borthakur, Gautam

AU - Gandhi, Varsha

AU - Kantarjian, Hagop M.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, may have off-target activity inducing acute myeloid leukemia (AML) differentiation, possibly through SYK inhibition. We investigated erlotinib in a pilot phase II study for efficacy in relapsed/refractory AML patients at a dose of 150 mg once daily in 28-day cycles. Twenty-nine patients were treated for a median of 29 days (range 12-142 days). Seven patients (24%) received > 1 cycle of therapy and 12 (41%) discontinued treatment before day 28 due to disease progression. One patient (3%) achieved complete remission and 2 (7%) a > 50% reduction in blasts. The most common toxicities associated with erlotinib were fatigue in 10 patients (34%), diarrhea in 10 (34%), nausea in 8 (28%), and rash in 7 (24%). Only 2 patients (7%) had study drug-related adverse events requiring dose reductions and eventual discontinuation. The main reason for treatment discontinuation was disease progression in 26 patients (90%). All patients had died by the time of the last follow-up. Progression of disease was the primary cause of death in all patients. Median overall survival was 14 weeks (range 2.3-96.9 weeks) and median event-free survival was 5 weeks (range 1.7-21.0 weeks). Erlotinib as a single agent has limited clinical efficacy in patients with relapsed/refractory AML.

AB - Erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, may have off-target activity inducing acute myeloid leukemia (AML) differentiation, possibly through SYK inhibition. We investigated erlotinib in a pilot phase II study for efficacy in relapsed/refractory AML patients at a dose of 150 mg once daily in 28-day cycles. Twenty-nine patients were treated for a median of 29 days (range 12-142 days). Seven patients (24%) received > 1 cycle of therapy and 12 (41%) discontinued treatment before day 28 due to disease progression. One patient (3%) achieved complete remission and 2 (7%) a > 50% reduction in blasts. The most common toxicities associated with erlotinib were fatigue in 10 patients (34%), diarrhea in 10 (34%), nausea in 8 (28%), and rash in 7 (24%). Only 2 patients (7%) had study drug-related adverse events requiring dose reductions and eventual discontinuation. The main reason for treatment discontinuation was disease progression in 26 patients (90%). All patients had died by the time of the last follow-up. Progression of disease was the primary cause of death in all patients. Median overall survival was 14 weeks (range 2.3-96.9 weeks) and median event-free survival was 5 weeks (range 1.7-21.0 weeks). Erlotinib as a single agent has limited clinical efficacy in patients with relapsed/refractory AML.

KW - Acute myeloid leukemia

KW - Erlotinib

KW - Relapsed/refractory AML

UR - http://www.scopus.com/inward/record.url?scp=85052652051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052652051&partnerID=8YFLogxK

U2 - 10.1159/000490092

DO - 10.1159/000490092

M3 - Article

C2 - 30071517

AN - SCOPUS:85052652051

VL - 140

SP - 30

EP - 39

JO - Acta Haematologica

JF - Acta Haematologica

SN - 0001-5792

IS - 1

ER -