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Abstract
Imiquimod is an immune response modifier with
potent antiviral and antitumour activity. The objective
of this pilot study was to evaluate the efficacy of an
imiquimod 5% cream (Aldara: 3M, Saint Paul, MN,
USA) as a topical treatment for equine sarcoids. Fifteen horses with a total of 19 tumours were enrolled,
including mixed (7), fibroblastic (5), flat (3), verrucous
(2), and nodular (2) types. Baseline data included
history, physical examination, tumour location, measurement and digital photography. Imiquimod was
applied by the owners three times a week until
complete resolution of the tumour or 32 weeks,
whichever occurred first. Tumours were measured
and photographed every 4 weeks. Treatment efficacy
was defined as 75% or greater reduction of tumour
size by the end of the trial. Four sarcoids were withdrawn from the study. Twelve of the remaining 15
tumours (80%) showed more than 75% reduction in
size and nine (60%) totally resolved between 8 and
32 weeks. The most common adverse effects of
exudation, erythema, erosions, depigmentation and
alopecia were limited to the tumour and adjacent
areas. The results suggest that topical imiquimod is
a therapeutic option for the treatment of equine
sarcoids, although more detailed studies are required
to corroborate these initial findings.
Accepted 19 April 2006
Introduction
Sarcoids, which vary clinically from benign flat to locally
aggressive ulcerative fibroblastic tumours,1 4 are very common neoplasms of horses worldwide, representing up to
90% of skin tumours and 20% of all tumours.1 3 Although
the cause is currently unknown, there is considerable
2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology. 17; 259265
259
Nogueira et al.
260
Table 1. Characteristics of 19 sarcoids from 15 horses included in the study
2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.
Tumours
Horse sex
Horse breed
Tumour types
Location of tumour
Age at onset
of tumour (years)
Age at first
visit (years)
Gelding
Quarter horse
Fibroblastic
Perineal region
16
20
2
3a
4a
5
6
7
8b
9b
10
11
12
13
14c
15c
16c
17
18
19
Mare
Mare
Quarter horse
Andalusian
Mare
Mare
Gelding
Gelding
Quarter horse
Appaloosa
Quarter horse
American Paint horse
Gelding
Gelding
Gelding
Gelding
Mare
Quarter horse
Arabian horse
Thoroughbred
Thoroughbred/Hanoverian
American Paint horse
Mare
Mare
Gelding
Thoroughbred
Arabian horse
Quarter horse
Fibroblastic
Verrucous
Mixed (flat + verrucous)
Flat
Verrucous
Flat
Mixed (flat + nodular)
Mixed (verrucous + nodular)
Nodular
Mixed (flat + nodular)
Fibroblastic
Fibroblastic
Mixed (flat + verrucous + nodular)
Nodular
Fibroblastic
Mixed (flat + nodular)
Flat
Mixed (flat + nodular)
Proximal limb
Thorax
Proximal limb
Neck
Pinna
Temporal region
Neck
Neck
Perineal region
Upper eyelid
Muzzle
Distal limb
Upper eyelid
Thorax
Distal limb
Neck
Proximal limb
Upper eyelid
5
18
18
19
24
10
4
4
11
2.5
13
1.5
4
4
4
2
15
4
7
23
23
24
29
15
6
6
13
4.5
15
3
6
6
6
4
16
5
Letters a, b and c identify the three horses with more than one treated tumours.
Previous therapies
Cryotherapy, laser, XXTERRA,
5-fluorouracil, cisplatin injection
Surgical removal twice
XXTERRA, surgical removal
None
None
XXTERRA, IV Eq-Stim
Nonspecific topical products
Antifungal oral therapy
Antifungal therapy
None
Surgical removal, XXTERRA
XXTERRA, nonspecific topical products
5-fluorouracil, surgical removal
Laser, cryotherapy
Laser, cryotherapy
Laser, cryotherapy
XXTERRA
None
None
Response to
previous therapies
Reoccurred
Reoccurred
Reoccurred
Reoccurred
No response
No response
No response
Reoccurred
No response
Reoccurred
No response
No response
Reoccurred
No response
Treatment protocol
A thin layer of imiquimod 5% cream (Aldara, 3M Pharmaceuticals,
Saint Paul, MN, USA) was applied to the tumour surface three times
a week on nonconsecutive days. Prior to application, the tumour was
cleaned with soap and water to remove exudate and improve drug
penetration. The first five horses were treated for 16 weeks, independent of treatment outcome, according to a human protocol.14
Based on the observations of these horses, duration of treatment was
extended for subsequent tumours until complete resolution or up to
32 weeks, whichever occurred first. The study protocol was approved
by the Animal Care and Use Committee of the University of Minnesota.
Withdrawal criteria
Horses were withdrawn from the study if there were intolerable
adverse effects that did not subside after 2 weeks of imiquimod
discontinuation or reduction in treatment frequency, lack of owner
compliance with treatment protocol or follow-up visits, concurrent
diseases that could interfere with treatment application or evaluation,
or owners desire to withdraw their horses.
Statistical analysis
Assuming that tumours are independent, a 95% confidence interval
(CI) for the success rate was estimated based on binomial distribution.
Statistical analysis was carried out using the SPSS statistical package
(SPSS version 11.5.1, Chicago, IL, USA).
Results
Treatment outcome
Four (21%) sarcoids were withdrawn from the trial upon
owners request: two after 4 weeks of therapy; one because
of inability to attend follow-up (tumour 6) and the other
because of winter treatment difficulty (tumour 7), and
two after 8 and 16 weeks of therapy (tumours 16c and 13,
respectively), because of lack of treatment response
(Table 2). Treatment was completed for 15 of the 19 (79%)
sarcoids. Twelve of the 15 sarcoids had more than 75%
reduction in size (Fig. 1a,b; Table 2), resulting in 80%
success rate (95% CI 60100%). Of these 12 sarcoids,
nine (60%) completely resolved (Fig. 2a,b; Table 2). The
time to achieve at least 75% reduction in size ranged from
8 to 32 weeks (Table 2). One flat, one verrucous and one
fibroblastic sarcoid (tumours 3a, 5 and 12; Table 2) failed
to respond to treatment. Upon completion of the study,
owners rated treatment efficacy as excellent in 11,
good in 3 and poor in 1 tumour. If the four withdrawn
sarcoids were included in the statistical analysis, it would
have resulted in a success rate of 68% (95% CI 58.8
79.1%).
2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.
261
Nogueira et al.
Table 2. Treatment outcome and follow-up of 19 sarcoids of various types treated with 5% imiquimod cream applied three times a week for up
to 32 weeks
Tumours
Tumour types
Baseline
A (cm2)
1*
Fibroblastic
252
2*
3a*
4a*
5*
6**
7**
8b
9b
10
11
12
13**
14c
15c
16c**
Fibroblastic
Verrucous
Mixed (flat + verrucous)
Flat
Verrucous
Flat
Mixed (flat + nodular)
Mixed (verrucous + nodular)
Nodular
Mixed (flat + nodular)
Fibroblastic
Fibroblastic
Mixed (flat + verrucous + nodular)
Nodular
Fibroblastic
17
18
19
Final
A (cm2)
Outcome
(% change
in size)
Duration of
treatment
(weeks)
Follow-up
time
(weeks)
97.62
16
28
8.75
24.5
36
266
4
78
12
45
2.38
10
6
22.5
3
12
10.5
0
15.75
8
104
1
91
0
0
0
0.2
9
34
0
0
12
100.00
35.71
77.78
60.90
75.00
16.67
100.00
100.00
100.00
98.00
50.00
51.11
100.00
100.00
14.29
16
16
16
16
4
4
16
16
16
32
32
16
12
16
8
60
28
28
24
45
60
32
32
36
23.2
8
0
8
8
4
15
27.5
1.8
0
0
0
100.00
100.00
100.00
12
8
8
4
4
12
Follow-up outcome
Restarted treatment
with imiquimod, stable
No recurrence
No change
No change
No change
No change
No change
No recurrence
No recurrence
No recurrence
No change
No change
Other therapy
No recurrence
No recurrence
Imiquimod after
debulking, reoccurred
No recurrence
No recurrence
No recurrence
A, cross-sectional area; , letters a, b and c identify the three horses with more than one treated tumours; , negative values indicate decrease in
size and positive signs indicate increase in size; *, tumours treated for 16 weeks independent of treatment outcome; **, withdrawn tumours.
2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.
Figure 3. Tumour 19. Mixed (flat and nodular) periorbital equine sarcoid. (a) At 4 weeks of imiquimod therapy showing severe exudate at
the tumour area, and alopecia and depigmentation on clinically normal
skin; (b) 4 weeks after imiquimod therapy showing almost complete
resolution of the side-effects with acceptable cosmetic outcome.
Discussion
In this pilot study, application of 5% imiquimod cream
(Aldara) once daily three times a week to equine sarcoids resulted in more than 75% reduction in tumour size
in 80% of the sarcoids. More frequent applications are
unlikely to have resulted in a higher or faster response
2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.
263
Nogueira et al.
This therapeutic efficacy of imiquimod seems to compare favourably with reported effects of intratumoural
administration of IL-2 and cisplatin, which showed partial
or complete regression in 80% of the sarcoids.2 On the
other hand, the percentage of completely resolved tumours
(60%) was somewhat lower than the rates reported for
local bacilli CalmetteGurin vaccination (64%), CO2 laser
(71%), cryosurgery (79%) and conventional surgical
excision (82%).9 This diversity may be a consequence of
differences in case selection and tumour location, size and
type. Possible insufficient treatment duration in this study
for the first four tumours treated for only 16 weeks could
have hindered a better final outcome. The results of this
study cannot be compared with topical therapies such as
XXTERRA, Animex, 5-fluorouracil and AW-3(4)-Ludes
where only anecdotal evidence of their efficacy has been
reported.1,6,12,13
In conclusion, results of this pilot study indicate that
imiquimod 5% cream is a convenient and safe option for
treatment of equine sarcoids. However, a prospective
randomized, double-blinded, placebo-controlled study
including larger number of different types of sarcoids is
needed.
Acknowledgements
The authors thank 3M Pharmaceuticals for drug supply,
Joan Lucas for motivation to pursue the study, Kathy
Stuebner for research coordination and Derek Knottenbelt
and Robert Koch for valuable manuscript review. They are
also grateful to both referring veterinarians and owners for
their contribution. This project was supported by the University of Minnesota Equine Center, College of Veterinary
Medicine, University of Minnesota, with funds provided
by the Minnesota Racing Commission, Minnesota Agricultural Experimental Station, and contributions from private
donors.
References
1. Scott DW, Miller WH. Neoplastic and non-neoplastic tumors. In:
Scott DW, Miller WH, eds. Equine Dermatology. Philadelphia, PA:
WB Saunders, 2003: 71931.
2. Spoormakers TJP, Klein WR, Jacobs JJL et al. Comparison of the
efficacy of local treatment of equine sarcoids with IL-2 or cisplatin/
IL-2. Cancer Immunology and Immunotherapy 2003; 52: 17984.
3. McConaghy FF, Davis RE, Hodgson DR. Equine sarcoid: a persistent therapeutic challenge. Compendium on Continuing Education
for the Practicing Veterinarian 1994; 16: 10229.
4. Foy JM, Rashmir-Raven AM, Brashier MK. Common equine skin
tumors. Compendium on Continuing Education for the Practicing
Veterinarian 2002; 24: 24254.
Rsum Limiquimod est un immunomodulateur avec des proprits antivirales et antitumorales. Lobjectif
de cette tude pilote tait dvaluer lefficacit dune crme 5% dimiquimod 5% cream (Aldara: 3M,
Saint Paul, MN) comme traitement topique des sarcodes du cheval. Quinze chevaux avec un total de 19
tumeurs ont t inclus, avec des sarcodes mixtes (7), fibroblastiques (5), plats (3), verruqueux (2), et
nodulaires (2). Les donnes tudies taient lanamnse, lexamen clinique, la localisation de la tumeur, la
taille, et des photographies digitales. Limiquimod tait appliqu par les propritaires trois fois par semaine
jusqu disparition complte de la tumeur ou pendant 32 semaines. Les tumeurs taient mesures et
photographies tous les mois. Le traitement tait considr efficace si la taille de la tumeur diminuait dau
moins 75% la fin de lessai. Quatre sarcodes sont sortis de lessai. Douze des quinze restants (80%) ont
264
2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.
diminu de plus de 75% et 9 (60%) ont totalement disparu entre 8 et 32 semaines. Les effets secondaires
les plus frquents taient une exudation, un rythme, des rosions, une dpigmentation et une alopcie
localiss la tumeur ou aux zones adjacentes. Ces rsultats suggrent que limiquimod par voie locale est
une option thrapeutique des sarcodes du cheval, bien que des tudes plus dtailles soient ncessaires
pour confirmer ces donnes.
Resumen Imiquimod es un modulador de la respuesta inmune con potente actividad antivrica y antitumoral. El objetivo de este estudio piloto fue evaluar la eficacia de una crema con un 5% de imiquimod
(Aldara: 3M, Saint Paul, MN) como tratamiento tpico para los sarcoides equinos. Quince caballos con
un total de 19 tumores fueron seleccionados, incluyendo los tipos mixto (7), fibroblstico (5), plano (3),
verrucoso (2) y nodular (2). La informacin clnica inicial incluy historia, examen fsico, localizacin de los
tumores, medidas y fotografa digital. La pomada de imiquimod se aplic por los propietarios tres veces en
semana hasta la curacin total del tumor o durante 32 semanas, lo que ocurriera antes. Los tumores fueron
medidos y fotografiados cada cuatro semanas. Un tratamiento efectivo se defini como aquel que produjo
una reduccin de un 75% o ms en el tamao del tumor al final del estudio. Cuatro de los sarcoides fueron
retirados del estudio. Doce de los restantes 15 (80%) presentaron una reduccin de ms de un 75% en el
tamao, y nueve (60%) resolvieron de forma completa entre las 8 y las 32 semanas. Los efectos adversos
mas comunes fueron exudacin, eritema, erosiones, depigmentacin y alopecia limitados al tumor y zonas
adjacentes. Los resultados sugieren que la pomada de imiquimod de aplicacin tpica es una opcin
terapetica para el tratamiento de los sarcoides equinos, aunque estudios ms detallados se requeriran
para confirmar estos hallazgos iniciales.
Zusammenfassung Imiquimod modifiziert die Immunantwort und besitzt starke antivirale und antitumorale
Aktivitt. Das Ziel dieser Pilotstudie war es, die Wirksamkeit einer 5%igen Imiquimod Crme (Aldara(tm):
3M, Saint Paul, MN) als topische Behandlung fr equine Sarkoide zu evaluieren. Fnfzehn Pferde mit
insgesamt 19 Tumoren wurden verwendet, diese setzten sich aus gemischten (7), fibroblastischen (5),
flachen (3), warzenartigen (2) und nodulren (2) Typen zusammen. Die Ausgangsdaten bestanden aus der
Anamnese, einer klinischen Untersuchung, der Lokalisation, Messung und digitalen Fotographie des Tumors.
Imiquimod wurde von den Besitzern drei mal wchentlich bis zum vlligen Verschwinden des Tumors oder
insgesamt fr 32 Wochen aufgetragen. Die Tumoren wurden alle vier Wochen gemessen und fotographiert.
Die Wirksamkeit der Behandlung wurde definiert mit einer 75% igen oder hheren Reduktion der Gre
des Tumors bei Studienende. Vier Sarkoide wurden aus der Studie genommen. Zwlf der brigen 15 (80%)
zeigten eine mehr als 75% ige Reduktion in Gre und 9 (60%) verschwanden zur Gnze nach 8 bis 32 Wochen.
Die hufigsten Nebenwirkungen wie Exudation, Erythem, Erosionen, Depigmentation und Alopezie waren
limitiert auf die Tumoren und angrenzenden Gebiete. Die Ergebnisse weisen darauf hin, dass topisches
Imiquimod eine therapeutische Option darstellt fr die Behandlung von equinen Sarkoiden, obwohl detailliertere Studien ntig sind, um diese anfnglichen Ergebnisse zu besttigen.
2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.
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