Journal Information
Vol. 99. Issue 1.
Pages 54-60 (January - February 2008)
Share
Share
Download PDF
More article options
Vol. 99. Issue 1.
Pages 54-60 (January - February 2008)
Original articles
Full text access
Adverse Cutaneous Reactions to Erlotinib
Efectos Cutáneos Adversos Causados Por Erlotinib
Visits
6930
G. Pitarcha,
Corresponding author
gerardpitarch@hotmail.com

Correspondence: Servicio de Dermatología, Hospital General de Castelló, Avda. Benicàssim s/n, 12004 Castelló de la Plana, Spain.
, J. Gardeb, A. Torrijosa, A. Juárezb, M.I. Febrera, C. Campsb
a Servicio de Dermatología, Consorci Hospital General Universitari de València, Valencia, Spain
b Servicio de Oncología Médica, Consorci Hospital General Universitari de València, Valencia, Spain
This item has received
Article information
Abstract
Introduction

Erlotinib is an inhibitor of human epidermal growth factor approved for treating nonsmall cell lung cancer. The aim of this prospective observational study was to determine the prevalence of adverse cutaneous reactions caused by erlotinib and assess the management of such effects.

Methods

Eleven patients with lung cancer and 1 with ovarian cancer received erlotinib at a dose of 150mg/d. The prevalence, severity, and time course of the adverse cutaneous reactions were assessed.

Results

The most frequent cutaneous reaction was acneiform eruption (10 cases). The patients were treated with topical erythromycin and clindamycin, or with doxycycline. Also reported were seborrheic dermatitis (5), paronychia (4), xerosis (3), mouth blisters (3), blepharitis (2), cheilitis (1), and fissures on the hands and feet (1). The first reactions to appear were seborrheic dermatitis (9.8 days until onset) and acneiform eruption (11.8 days), whereas the paronychia presented latest (65.3 days). One patient with acneiform eruption and another with paronychia suspended treatment until the lesions improved.

Conclusions

Erlotinib induces adverse effects in most patients treated. Acneiform eruption, seborrheic dermatitis, and paronychia are the most frequently reported reactions and can lead to temporary suspension of erlotinib administration.

Key words:
erlotinib
epidermal growth factor receptor
acneiform
seborrheic dermatitis
paronychia
Resumen
Introducción

El erlotinib es un inhibidor del factor de crecimiento epidérmico humano aprobado en el tratamiento del cáncer de pulmón no microcítico. El objetivo de este estudio prospectivo y observacional es determinar la prevalencia de los efectos cutáneos adversos por erlotinib y su manejo.

Métodos

Once pacientes con cáncer de pulmón y una con cáncer de ovario fueron tratados con erlotinib en dosis de 150 mg diarios. Se evaluó la prevalencia, la intensidad y la cronología de los efectos cutáneos adversos.

Resultados

La reacción cutánea más frecuente fue la erupción acneiforme (10 casos). Los pacientes fueron tratados con eritromicina o clindamicina tópicas, o con doxicilina. Los pacientes también desarrollaron dermatitis seborreica (5), paroniquia (4), xerosis (3), aftas orales (3), blefaritis (2), queilitis (1) y fisuras en manos y pies (1). Los efectos adversos más precoces fueron la dermatitis seborreica (9,8 días hasta la aparición) y la erupción acneiforme (11,8 días), mientras que la paroniquia fue el efecto más tardío (65,3 días). Un paciente con erupción acneiforme y otro con paroniquia suspendieron el tratamiento con erlotinib hasta la mejoría de las lesiones.

Conclusiones

El erlotinib produce efectos cutáneos adversos en la gran mayoría de los pacientes tratados. La erupción acneiforme, la dermatitis seborreica y la paroniquia son los efectos más frecuentes, que pueden llevar a interrumpir temporalmente la administración de erlotinib.

Palabras clave:
erlotinib
receptor de factor de crecimiento epidérmico
acneiforme
dermatitis seborreica
paroniquia
Full text is only aviable in PDF
References
[1.]
F. Ciardello, G. Tortora.
Anti-epidermal growth factor receptor drugs in cancer therapy.
Expert Opin Investig Drugs, 11 (2002), pp. 755-768
[2.]
L.B. Saltz, N.J. Meropol, P.J. Loehrer Sr, M.N. Needle, J. Kopit, R.J. Mayer.
Phase II Trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor.
J Clin Oncol, 22 (2004), pp. 1201-1208
[3.]
M.G. Kris, R.B. Natale, R.S. Herbts, T.J. Lynch Jr, D. Prager, C.P. Belani, et al.
Efficacy of gefitinib, an inhibitor of the epidermal growth factor tyrosine kinase, in symptomatic patients with non-small lung cancer: A randomized trial.
JAMA, 290 (2003), pp. 2149-2158
[4.]
R. Pérez-Soler, A. Chachoua, L.A. Hammond, E.K. Rowinsky, M. Huberman, D. Karp, et al.
Determinants of tumor response and survival with erlotinib in patients with non–small-cell lung cancer.
J Clin Oncol, 22 (2004), pp. 3238-3247
[5.]
S.S. Sridhar, L. Seymour, F.A. Shepherd.
Inhibitors of epidermalgrowth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer.
Lancet Oncol, 4 (2003), pp. 397-406
[6.]
M.H. Nelson, C.R. Dolder.
Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors.
Ann Pharmacother, 40 (2006), pp. 261-269
[7.]
G. Blackledge, S. Averbuch.
Gefitinib (’Iressa’, ZD1839) and new epidermal growth factor receptor inhibitors.
Br J Cancer, 90 (2004), pp. 566-572
[8.]
M.W. Lee, C.W. Seo, S.W. Kim, H.J. Yang, H.W. Lee, J.H. Choi, et al.
Cutaneous side effects in non-small cell lung cancer patients treated with Iressa (ZD1839), an inhibitor of epidermal growth factor.
Acta Derm Venereol, 84 (2004), pp. 23-26
[9.]
M. Fernández-Galar, A. España, J.M. López-Picazo.
Acneiform lesions secondary to ZD1839, an inhibitor of the epidermal growth factor receptor.
Clin Exp Dermatol, 29 (2004), pp. 138-140
[10.]
I. Kurokawa, K. Endo, M. Hirabayashi.
Purpuric drug eruption possibly due to gefitinib (Iressa.).
Int J Dermatol, 44 (2005), pp. 167-168
[11.]
J.C. Pascual, J. Bañuls, I. Belinchon, M. Blanes, B. Massuti.
Trichomegaly following treatment with gefitinib (ZD1839).
Br J Dermatol, 151 (2004), pp. 1111-1112
[12.]
L. Walon, C. Gilbeau, J.M. Lachapelle.
Éruptions acnéiformes induites par le cétuximab.
Ann Dermatol Venereol, 130 (2003), pp. 443-446
[13.]
W. Jacot, D. Bessis, E. Jorda, M. Ychou, M. Fabbro, J.L. Pujol, et al.
Acneiform eruption induced by epidermal growth factor inhibitors in patients with solid tumours.
Br J Dermatol, 151 (2004), pp. 238-241
[14.]
K.J. Busam, P. Capodieci, R. Motzer, T. Kiehn, D. Phelan, A.C. Halpern.
Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225.
Br J Dermatol, 144 (2001), pp. 1169-1176
[15.]
R. Van Doorn, G. Kirtschig, E. Scheffer, T.J. Stoof, G. Giaccone.
Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor.
Br J Dermatol, 147 (2002), pp. 598-601
[16.]
E. Herrera-Acosta, G. Martín-Ezquerra, M. Iglesias, P. Umbert.
Erupción acneiforme secundaria a cetuximab.
Actas Dermosifiliogr, 96 (2005), pp. 252-254
[17.]
J.M. Isarría, I. Alonso, A. Segurado, J. Ortiz, F. Vanaclocha.
Reacción cutánea secundaria a tratamiento con Iressa (ZD 1839).
Actas Dermosifiliogr, 95 (2004), pp. 459-461
[18.]
M.H. Cohen, J.R. Johnson, Y.F. Chen, R. Sridhara, R. Pazdur.
FDA drug approval summary: erlotinib (Tarceva.) tablets.
Oncologist, 10 (2005), pp. 461-466
[19.]
M. Hidalgo, L. Siu, J. Nemunaitis, J. Rizzo, L.A. Hammond, C. Takimoto, et al.
Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies.
J Clin Oncol, 19 (2001), pp. 3267-3279
[20.]
G.M. Clark, R. Pérez-Soler, L. Siu, A. Gordon, P. Santabarbara.
Rash severity is predictive of increased survival with erlotinib HCl.
Proc Am Soc Clin Oncol, 22 (2003), pp. 196
[21.]
D. Soulieres, N.N. Senzer, E.E. Vokes, M. Hidalgo, S.S. Agarwala, L.L. Siu.
Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck.
J Clin Oncol, 22 (2004), pp. 77-85
[22.]
R. Pérez-Soler.
Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome?.
Oncology (Huntingt), 17 (2003), pp. 23-28
[23.]
R. Pérez-Soler.
The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer.
Clin Cancer Res, 10 (2004), pp. 4238S-4240S
[24.]
L.E. King Jr, R.E. Gates, C.M. Stoscheck, L.B. Nanney.
The EGF/TGF alpha receptor in the skin.
J Invest Dermatol, 94 (1990), pp. 164S-170S
[25.]
R. Bruno, R.D. Mass, C. Jones, J.F. Lu, E. Winer.
Preliminary population pharmacokinetics (PPK) and exposure-safety (ES) relationships of erlotinib HCl in patients with metastatic breast cancer (MBC).
Proc Am Soc Clin Oncol, 22 (2003), pp. 205
[26.]
R. Pérez-Soler, L. Saltz.
Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining?.
J Clin Oncol, 23 (2005), pp. 5235-5246
[27.]
J. Albanell, F. Rojo, S. Averbuch, A. Feyereiskova, J.M. Mascaro, R. Herbst, et al.
Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition.
J Clin Oncol, 20 (2002), pp. 110-124
[28.]
A.N. Sapadin, R. Fleischmajer.
Tetracyclines: nonantibiotic properties and their clinical implications.
J Am Acad Dermatol, 54 (2006), pp. 258-265
[29.]
M.R. Green, J.R. Couchman.
Differences in human skin between the epidermal growth factor receptor distribution detected by EGF binding and monoclonal antibody recognition.
J Invest Dermatol, 85 (1985), pp. 239-245
[30.]
N.T. Shah, M.G. Kris, W. Pao, L.B. Tyson, B.M. Pizzo, M.H. Heinemann, et al.
Practical management of patientswith non-small-cell lung cancer treated with gefitinib.
J Clin Oncol, 23 (2005), pp. 165-174
[31.]
S. Dueland, T. Sauer, F. Lund-Johansen, B. Ostenstad, K.M. Tveit.
Epidermal growth factor receptor inhibition induces trichomegaly.
Acta Oncol, 42 (2003), pp. 345-346
[32.]
T. Dainichi, M. Tanaka, N. Tsuruta, M. Furue, K. Noda.
Development of multiple paronychia and periungual granulation in patients treated with gefitinib, an inhibitor of epidermal growth factor receptor.
Dermatology, 207 (2003), pp. 324-325
[33.]
S. Segaert, E. Van Cutsem.
Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors.
Ann Oncol, 16 (2005), pp. 1425-1433
[34.]
K.Y. Suh, H.L. Kindler, M. Medenica, M. Lacouture.
Doxycycline for the treatment of paronychia induced by the epidermal growth factor receptor inhibitor cetuximab.
Br J Dermatol, 154 (2006), pp. 191-192
Copyright © 2008. Academia Española de Dermatología y Venereología and Elsevier España, S.L.
Download PDF
Idiomas
Actas Dermo-Sifiliográficas
Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?