McNeill et al 2009 Evaluation of Adjuvant

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Evaluation of Adjuvant Doxorubicin-Based Chemotherapy for the
Treatment of Fel ine Mammary Carcinoma
C.J.McNeill, K.U. Sorenmo, F.S. Shofer, L. Gibeon, A.C. Durham, L.G. Barber, J.L. Baez, and B. Overley
Background: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high
metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate
the effect of this strategy.
Hypothesis: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone.
Animals: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus
adjuvant doxorubicin-based chemotherapy (Sx 1 Chemo).
Methods: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups.
Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were
evaluated.
Results: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx 1 Chemo group. No differ-
ences in clinical data were found between Sx and Sx 1 Chemo groups. Median DFS times for the Sx and Sx 1 Chemo groups
were 372 and 676 days, respectively (P 5 .15) and median survival times (ST) were 1,406 and 848 days, respectively (P 5 .78).
For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx1 Chemo compared with the Sx
group (1,998 versus 414 days, respectively; P5 .03).
Conclusions and Clinical Importance: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats
with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may ben-
efit from adjuvant chemotherapy.
Key words: Adriamycin; Breast; Cancer; Cat; Surgery.
Mammary carcinoma is the 3rd most common can-cer in cats, affecting mainly females with a mean
age at diagnosis of 10–12 years.1–6 Approximately 90%
of mammary tumors in cats are malignant.7–10 The be-
havior of these tumors is characterized by local invasion
into the vasculature and surrounding tissues and by me-
tastasis to distant locations, including the draining lymph
nodes, lungs, and other sites.1–3,5,6,8,9,11–13
Risk factors for development of feline mammary car-
cinoma (FMC) include breed, a history of long-term
progestin treatment, and age at ovariohysterecto-
my.2,3,14–16 Prognostic factors for FMC include tumor
size, advanced clinical stage, tumor grade, histologic sub-
type, extent of surgery, location of metastases, loss of
estrogen receptor status, and increased expression of
vascular endothelial growth factor, human epithelial
receptor-2 (HER2/neu), argyrophilic nucleolar organizer
region, proliferating cell nuclear antigen counts, cycloox-
ygenase-2, and Ki-67 index.4,6,17–29
Radical surgical excision traditionally has been the
treatment of choice for FMC and results in a reduction in
recurrence rate but no difference in overall survival time
(ST) compared with treatment with conservative sur-
gery.9,17 Cats with small tumors (o2 cm in diameter) are
reported to have a long survival (up to 54 months) after
surgery.4,6,17,18 Complete surgical intervention therefore
may prove adequate for treatment of small tumors, and
adjuvant chemotherapy may not be necessary. However,
for cats with larger tumors, postoperative survival is re-
ported to be o1 year and many of these cats die from
metastatic disease.4,6,17,18 These cats therefore may ben-
efit from adjuvant chemotherapy.
Chemotherapy protocols commonly used for FMC in-
clude doxorubicin as a single agent or in combination
with cyclophosphamide.19,30,31 Most reports, however,
have only assessed tumor response in the bulky tumor
setting of FMC, and there are few reports that have
evaluated the effect of adjuvant chemotherapy after
surgery has been performed.30,31 A recent study reported
prolonged STs in cats treated with surgery followed by
chemotherapy but did not determine the actual role of
adjuvant doxorubicin chemotherapy, because the study
did not include a control population.19
The purpose of this study was to test the hypothesis
that adjuvant doxorubicin-based chemotherapy im-
proves outcome for FMC compared with surgery alone.
Materials and Methods
A retrospective cohort study of all FMC cases diagnosed over 17
years (1989–2006) was performed at 6 veterinary referral institu-
tions and 3 general practices with specialty interests in feline
medicine and surgery. These included the Cat Clinic at Cherry Hill
From the Department of Clinical Studies, Matthew J. Ryan Vet-
erinary Hospital, University of Pennsylvania, Philadelphia, PA
(McNeill, Sorenmo, Shofer, Gibeon, Overley); the Department of
Pathobiology, School of Veterinary Medicine, University of Pennsyl-
vania, Philadelphia, PA (Durham); the Department of Clinical
Sciences, Cummings School of Veterinary Medicine, Tufts Univer-
sity, North Grafton, MA (Barber); and the Center for Animal
Referral and Emergency Services, Langhorne, PA (Baez). Dr Gibe-
on is presently affiliated with the NYC Veterinary Specialists, New
York, NY. Data presented in part at the 26th Annual Conference of
the Veterinary Cancer Society, Pine Mountain, GA, October 19–22,
2006.
Corresponding author: Conor J. McNeill, DVM, DACVIM
(Oncology), Department of Clinical Studies, Matthew J. Ryan Vet-
erinary Hospital, University of Pennsylvania, 3900 Delancey Street,
Philadelphia, PA 19104-6010; e-mail: cmcneill@vet.upenn.edu.
Submitted November 28, 2007; Revised March 12, 2008; Revised
July 30, 2008;Revised October 22, 2008; Accepted October 30, 2008.
Copyright r 2009 by the American College of Veterinary Internal
Medicine
10.1111/j.1939-1676.2008.0244.x
J Vet Intern Med 2009;23:123–129
(Cherry Hill, NJ); the Center for Animal Referral and Emergency
Services (Langhorne, PA); Davies Veterinary Specialists (Higham
Gobion, Hertfordshire, UK); the Foster Hospital for Small Animals
of the Cummings School of VeterinaryMedicine at Tufts University
(North Grafton, MA); Old Marple Veterinary Hospital (Spring-
field, PA); the Matthew J. Ryan Veterinary Hospital of the
University of Pennsylvania (Philadelphia, PA); Red Bank Veteri-
nary Hospital (Tinton Falls, NJ); the University of California at
Davis Veterinary Medical Teaching Hospital (Davis, CA); and the
VCA Cat Hospital of Philadelphia (Philadelphia, PA).
Information was collected from medical records, referring and
treating veterinarians, and telephone interviews with owners. Crite-
ria for inclusion were surgical excision of the primary tumor and
any lymph nodes with metastases and a confirmed diagnosis of
mammary carcinoma by a veterinary pathologist. The cats were
categorized into 2 groups based on treatment: the 1st group (Sx)
consisted of cats treated with surgery alone and the 2nd (Sx 1
Chemo) consisted of cats treated with surgery plus adjuvant do-
xorubicin-based chemotherapy.
Adjuvant chemotherapy in this study was defined as chemother-
apy treatment after definitive surgery to remove the primary tumor
and before any recurrence or progression. Acceptable chemother-
apy protocols included single agent doxorubicin or doxorubicin in
combination with cyclophosphamide. Cats treated with other che-
motherapeutic agents before progression of the FMCwere excluded
from the study. Concurrent treatment with prednisone, antibiotics,
or other drugs unlikely to affect tumor progression or outcome was
permitted.
Information regarding clinical characteristics such as breed, sex,
neuter status, age at diagnosis, tumor characteristics, and presence
and location of metastases was collected. If performed, diagnostic
staging before surgery included physical examination, CBC, serumbiochemical profile, lymph node aspiration of palpably enlarged
lymph nodes, thoracic radiographs, and abdominal ultrasound ex-
amination. Cats were staged according to modified World Health
Organization staging criteria (Table 1). Cats with confirmed distant
metastatic disease were excluded from the study. Lymph nodes were
considered positive for metastasis if they were found to be palpably
enlarged and infiltrated on cytology or histopathology. Lymph
nodes were considered negative if no evidence of metastasis was
found on cytology or histopathology of the node, if lymph nodes
were reported to be palpably normal, or if they were not removed
and not reported abnormal on physical examination. Tumor mea-
surements also were recorded.
Additional information recorded included the date of definitive
surgery, whether surgery was performed at a general practice or re-
ferral institution, type of surgery performed (local versus radical),
date of 1st documented disease progression, and date of death. The
reason for euthanasia or cause of death also was recorded.
Disease-free survival (DFS) was defined as the time interval be-
tween date of diagnosis and 1st documentation of disease
progression (either metastatic disease or local recurrence). ST was
defined as the time interval between date of diagnosis and date of
death. Cats that were alive or died from causes unrelated to FMC
were censored at the last date they were reported to be alive.
To determine differences between treatment groups, the Fisher
exact test or w2 test was used for categorical data. The Student’s
t-test was used to analyze continuous data. Curves for DFS and
overall STs were generated using the Kaplan-Meier product-limit
method. Differences in overall survival or DFS between groups
were tested using the log-rank test. A P-valueo .05 was considered
statistically significant. All data were analyzed by SASa statistical
software.
Results
Clinical Variables
Seventy-three cats were included in the study. There
were 37 (51%) cats in the surgery only (Sx) group and 36
(49%) cats in the surgery followed by chemotherapy (Sx
1 Chemo) group. The mean age at diagnosis was 11.1
years (range, 3–18; Sx mean, 11.4 years; Sx 1 Chemo
mean, 10.9 years, P 5 .47). Mean age at ovariohysterec-
tomy was 5.6 years (range, 0.3–14.1 years; n 5 30) and
was not significantly different between groups (P 5 .45).
Domestic short hair cats were the most common breed,
and the majority of cats were spayed females (Table 2A).
In terms of staging diagnostics performed, 64 (88%)
cats had a CBC, 65 (89%) cats had a serum biochemical
profile, 67 (92%) cats had preoperative thoracic radiog-
raphy, and 23 (32%) cats had abdominal ultrasound
examination performed.
Tumor Characteristics
Overall mean tumor size was 1.7 cm in diameter
(range, 0.25–5 cm). Forty-seven percent of cats had tu-
mor size o 2 cm in diameter without reported evidence
of spread to regional lymph nodes. Twenty-five (68%)
cats in the Sx group and 19 (53%) cats in the Sx 1
Chemo group had tumors measuringo2 cm in diameter
(Table 2B). Seventeen (23%) cats had evidence of meta-
static spread to the regional lymph nodes, all of which
were removed at time of surgery. One cat had an enlarged
lymph node without evidence of metastatic spread.
Histologic characteristics of the FMC were compared
between the treatment groups as shown in Table 2B.
There were no significant differences between groups
with regard to tumor size or histologic findings, which
included clean surgical margins, vascular invasion, or
metastasis to the draining lymph node.
Treatments
Forty-three (59%) cats had surgery performed at a
general practice hospital (Table 2B). Thirty-three (45%)
cats had a radical mastectomy, of which 15 (45%) were
bilateral. There were no significant differences between
treatment groups with regard to the type of hospital
where surgery was performed or surgical procedure for
Table 1. Staging classification of feline mammary gland
tumors.a
Stage T N M
I T1 N0 M0
II T2 N0 M0
III T1,2
T3
N1
N0,1
M0
M0
IV Any T Any N M1
aModified from ref. 32.
T, primary tumor; T1, o 2 cm maximum diameter; T2, �2 to o
3 cm maximum diameter; T3, �3 cm maximum diameter; N, re-
gional lymph node; N0, no histologic/cytologic metastasis; N1,
histologic/cytologic metastasis; M, distant metastasis; M0, no evi-
dence of metastasis; M1, evidence of metastasis.
124 McNeill et al
removal of the mammary tumor. All cats received che-
motherapy at referral hospitals. The median interval time
from diagnosis to the start of chemotherapy was 27 days
(range, 6–102 days). Four cats received doxorubicin as a
single agent, with the remaining cats treated initially with
a combination of doxorubicin and cyclophosphamide.
The number of doses of doxorubicin varied from 5 (n 5
3) to 4 (n 5 21), 3 (n 5 5), 2 (n 5 3), and 1 (n 5 4). The
number of cyclophosphamide treatments also varied
from 5 (n 5 1) to 4 (n 5 16), 3 (n 5 4), 2 (n 5 4), and 1
(n 5 7). Overall, 81% of the cats in this group received
�3 cycles of treatment.
Outcome
Metastases or local recurrence developed in 36 (49%)
cats (Table 3). The most common site of disease progres-
sion was the original surgery site or another mammary
gland, followed by the lungs, the draining lymph node,
the pleural space (effusion), and abdominal organs.
There were no significant differences between groups in
terms of location of metastases. The extent of the surgical
procedure did not affect the frequency of local recurrence
in either treatment group (Sx, P 5 .48; Sx 1 Chemo,
P 5 .51).
Table 2. Analysis of feline mammary carcinoma cases.
Total Sx Sx1 Chemo
n % n % n %
(A) Population distribution
Total 73 100 37 51 36 49
Breed
Domestic shorthair 52 71 26 70 26 72
Domestic longhair 6 8 3 8 3 8
Siamese 3 4 3 8 0 0
Other breeds 12 16 5 14 7 19
Sex
Female spayed 64 88 32 86 32 89
Female unspayed 3 4 2 5 1 3
Male castrated 6 8 3 8 3 8
Total Sx Sx1 Chemo
P-Valuen % n % n %
(B) Tumor characteristics
Size (cm)
o 2 44 60 25 68 19 53 .43
�2 too 3 10 14 4 11 6 17
�3 19 26 8 22 11 31
Aspect
Ulcerated 8 11 5 14 3 8 .71
Histologic data
Lymphatic invasion 21 29 12 32 9 25 .60
Vascular invasion 6 8 4 11 2 6 .67
Tumor at margins 11 15 4 11 7 19 .33
Metastasis to regional lymph node 17 23 6 16 11 31 .17
Surgical factors
Location
Specialist 30 41 13 35 17 47 .35
Type
Radical surgery 33 45 13 35 20 56 .10
Radical bilateral 15 21 3 8 12 33 .07
Frequency is given in percentages. Po .05 is considered statistically significant. (A) Population distribution. (B) Tumor characteristics.
Sx, surgery alone; Sx1 Chemo, surgery plus adjuvant doxorubicin-based chemotherapy.
Table 3. Location of disease progression of feline mam-
mary carcinoma.
Total Sx Sx1 Chemo
P-Valuen % n % n %
Progression 36 49 20 54 16 44 .49
Locations
Local (mammary) 31 86 18 90 13 81 .35
Lungs 15 42 9 45 6 38 .56
Draining lymph nodes 8 22 5 25 3 19 .71
Pleural space (effusion) 6 17 5 25 1 6 .20
Abdominal organs 4 11 2 10 2 13 1.0
Frequency is given in percentages. Po .05 is considered statisti-
cally significant.
Sx, surgery alone; Sx 1 Chemo, surgery plus adjuvant do-
xorubicin-based chemotherapy.
125Chemotherapy Feline Mammary Carcinoma
Twenty-one of the 36 cats (Sx, n5 13; Sx1 Chemo, n
5 8) that relapsed received rescue treatment. Nine cats
underwent a 2nd surgery, 5 received rescue chemother-
apy without surgery, and 7 underwent both a 2nd surgery
and rescue chemotherapy.
Median follow-up time for all cats was 396 days
(range, 6–1,998 days). Reasons for premature cessation
of treatment were not always available from patient re-
cords. In the Sx group, 1 cat was censored as lost to
follow-up at 6 days postsurgery. Nineteen(51%) cats in
the Sx group and 15 (42%) in the Sx 1 Chemo group
were alive at the time of last known contact. Four cats in
the Sx group and 5 cats in the Sx1 Chemo group died of
unrelated causes without evidence of progression. One
cat in the Sx group developed a local recurrence of FMC
but was euthanized after complications of a nonhealing
suppurative wound in its digit. These cats were censored
from the survival analysis at their time of death. Thirteen
(35%) cats in the Sx group and 16 (44%) in the Sx 1
Chemo group died or were euthanized as a consequence
of FMC. Necropsies were performed on 3 (4%) cats, all
of which were in the Sx 1 Chemo group. Postmortem
examination identified local recurrence of carcinoma in 1
cat and metastatic spread (pleura, lungs, lymph nodes,
thyroid gland, adrenal glands, kidneys, and heart) in the
other 2 cats.
Median DFS for the Sx cats was 372 days compared
with 676 days (P 5 .15) for the Sx 1 Chemo group (Fig
1). Median ST for Sx cats and Sx 1 Chemo cats were
1,406 and 848 days (P5 .78), respectively (Fig 2).
In the subgroups of cats with tumors measured aso2,
�2 to o3, or � 3 cm in diameter, no significant differ-
ences in DFS (Table 4) or ST (Table 5) among groups
were identified. No significant differences in outcome
were found when comparing other tumor characteristics,
including ulceration, vascular invasion, or regional
lymph node metastasis. When comparing the type of
practice where the surgery was performed, no differences
in outcome were identified. However, when comparing
the type of surgery performed, the subgroup of cats that
underwent a radical unilateral surgery had a significantly
longer ST in the Sx1 Chemo group than in the Sx group
(1,998 versus 414 days, respectively; P 5 .03).
Discussion
Adjuvant chemotherapy is commonly recommended
for the treatment of FMC. However, to date, few studies
have evaluated the benefit of adjuvant chemotherapy.
The present study questions the benefit of this recom-
mendation.
To the authors’ knowledge, this is the 1st study to in-
clude a control group to test the benefit of adjuvant
chemotherapy. Compared with results from a recent re-
port on adjuvant doxorubicin chemotherapy in FMC,
DFS (676 versus 255 days) and overall ST (848 versus 448
days) were longer in the current study.19 Comparison
with a control group did not identify an overall benefit to
adjuvant chemotherapy. This result could be because
there may be no clear benefit. The wide and overlapping
confidence intervals indicate great variability in outcome
among individuals within each group. The previous re-
port suggested that bilateral radical mastectomy
improved median disease-free interval, but the current
study was unable to confirm this benefit. We may have
missed this benefit owing to the small sample sizes avail-
able in the subgroup evaluation or the fact that the
majority of patients in the subgroup analysis were cen-
sored at the study’s end. Therefore, caution should be
used in interpreting these results.
In the present study, the Sx and Sx 1 Chemo groups
were equivalent based on evaluated clinical variables.
However, the study design had limitations that could
have biased the outcome results. It was not a randomized
study and was retrospective in nature and thus dependent
on historical data. Complete clinical data were not al-
ways entered in the medical records and follow-up was
not performed at standard intervals. Cats from multiple
institutions, both from specialty and general practices,
were combined with possible variability in staging diag-
nostics. In addition, only palpably enlarged lymph nodes
were sampled to confirm metastatic disease. Conse-
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Months
0.0
0.2
0.4
0.6
0.8
1.0
Pr
op
or
tio
n 
D
is
ea
se
 F
re
e Sx
Chemo & Sx
Fig 1. Kaplan-Meier survival analysis for disease-free survival
(DFS). P o .05 is considered statistically significant. Median DFS
in days of Sx (n5 37; 372 days) and Sx1 Chemo (n5 36; 676 days,
P5 .15). Sx, surgery alone; Sx1 Chemo, surgery plus adjuvant do-
xorubicin-based chemotherapy.
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
Months
0.0
0.2
0.4
0.6
0.8
1.0
Pr
op
or
tio
n 
Su
rv
ivi
ng
Sx
Chemo & Sx
Fig 2. Kaplan-Meier survival analyses for overall survival. P o
.05 is considered statistically significant. Median survival times in
days of Sx (n5 37; 1,406 days) and Sx1 Chemo (n5 36; 848 days,
P5 .78). Sx, surgery alone; Sx1 Chemo, surgery plus adjuvant do-
xorubicin-based chemotherapy.
126 McNeill et al
quently, possible (microscopic) metastatic disease to the
draining lymph nodes could have been underdiagnosed.
There was a potential for referral bias in the chemother-
apy group, because these cats all were treated in referral
hospitals, which might have selected for a different
owner type. These owners might have chosen to pursue
more aggressive treatment and might have been less will-
ing to consider cessation of treatment, which could have
affected the ST in this group. Also, these cats would have
had more frequent follow-up and monitoring during
Table 4. Analysis of effect of tumor characteristics and surgical factors on disease-free survival for FMC.
Sx Sx1 Chemo
P-Valuen DFS 95% CI n DFS 95% CI
Overall 37 372 142–1260 36 676 435-1960 .15
Tumor size (cm)
o 2 25 265 115–1260 19 509 435–676 .65
�2–o 3 4 403 49–NR 6 1960 407–1960 .50
�3 8 558 60–NR 11 NR 250–NR .24
Surgery
General practitioner 24 403 111–NR 19 563 407–NR .48
Referral hospital 13 328 166–NR 17 1138 435–1960 .21
Procedure
Local 24 403 166–NR 16 563 250–NR .42
Radical 13 328 94–793 20 676 435–1960 .09
Radical unilateral 10 115 94–558 8 1960 509–1960 .05
Radical bilateral 3 793 49–793 12 435 379–1,138 .85
Tumor
Ulcerated 5 NR 22–NR 3 NR NR .19
Histologic data
Lymphatic invasion 12 166 55–NR 9 407 132–491 .91
Vascular invasion 4 55 22–243 2 NR 132–NR .30
Tumor at margins 4 106 43–NR 7 407 175–1960 .93
Metastasis to regional lymph node 6 166 49–793 11 250 145–435 .67
Results shown are median number of days with 95% confidence intervals (CI).
NR: median DFS not reached (more than half the cats were censored at study end). Po .05 considered statistically significant.
DFS, disease-free survival; FMC, feline mammary carcinoma; Sx, surgery alone; Sx 1 Chemo, surgery plus adjuvant doxorubicin-based
chemotherapy.
Table 5. Analysis of effect of tumor characteristics and surgical factors on survival time for FMC.
Sx Sx1 Chemo
P-Valuen ST 95% CI n ST 95% CI
Overall 37 1,406 376–NR 36 848 616–1751 .78
Tumor size (cm)
o 2 25 611 376–NR 19 729 496–848 .48
�2–o 3 4 NR 67–NR 6 1,998 616–1,998 .83
�3 8 NR 144–NR 11 1,751 1,341–NR .23
Surgery
General practitioner 24 1,406 611–NR 19 729 496–1,341 .43
Referral hospital 13 376 266–NR 17 892 516–1,998 .28
Procedure
Local 24 1,406 454–NR 16 729 496–NR .47
Radical 13 414 203–NR 20 892 616–1,998 .16
Radical unilateral 10 414 266–NR 8 1,998 NR .03
Radical bilateral 3 NR 67–NR 12 761 476–1,751 .90
Tumor
Ulcerated 5 454 77–454 3 NR NR .19
Histologic data
Lymphatic invasion 12 353 284–NR 9 616 354–761 .97
Vascular invasion 4 284 77–454 2 NR 354–NR .50
Tumor at margins 4 NR 203–NR 7 616 354–729 .56
Metastasis to regional lymph node 6 353 67–NR 11 476 339–848 .88
Results shown are median number of days with 95% confidence intervals (CI). Po .05 considered statistically significant. NR: median ST
not reached (more than half the cats were censored at study end).
ST, survival time; FMC, feline mammary carcinoma; Sx, surgery; Sx 1 Chemo, surgery plus adjuvant doxorubicin-based chemotherapy.
127Chemotherapy Feline Mammary Carcinoma
their chemotherapy treatment. Any recurrences or me-
tastases would have been found earlier at the regularvisits, which might have shortened the DFS in this group.
Only 3 cats in the Sx 1 Chemo group had necropsy per-
formed. The evaluation of metastatic locations in the
other euthanized or censored cats likely is underreported.
All cats in the study had FMC confirmed by histopa-
thology. However, evaluations in this study were not
performed for additional known negative prognostic in-
dicators in FMC, including tumor grade, histologic
subtype, steroid receptor, and HER2/neu status. There-
fore, the possible influence of these factors on outcome in
this population could not be assessed.
Median time from diagnosis and surgery to the start of
chemotherapy waso1 month. However, this time inter-
val was variable, and some cats experienced a prolonged
time interval between surgery and start of chemotherapy.
Delay of treatment might allow time for micrometastatic
disease to emerge, and could have adversely affected the
success of chemotherapy in some patients included in this
study.
The inclusion criteria of this study may have contrib-
uted to a selection bias in this population and obscured
evidence of a true benefit from adjuvant chemotherapy in
FMC. Although the purpose of this study was to evalu-
ate the benefit of chemotherapy for FMC in the adjuvant
setting, almost half of the cats (47%) in this study pop-
ulation had only small tumors and did not have clinical
evidence of metastasis. Such cats generally are reported
to have a good outcome with surgery alone.17 In con-
trast, increased tumor size has been shown to be a
negative prognostic factor, and it is these cats in partic-
ular that would theoretically benefit most from adjuvant
chemotherapy. Thus, subgroups with known negative
prognostic factors also were evaluated separately. How-
ever, even in the resultant subgroups, the confidence
intervals were wide and the results were not statistically
different. Only a small number of cats with large tumors
(26%, n 5 19) or metastatic disease at time of diagnosis
(23%, n5 17) were evaluated in this study. With the cur-
rent sample size, there was only a 12% power to detect
the difference found between treatment groups.
The results of this study suggest that the use of adjuv-
ant doxorubicin chemotherapy for FMC needs further
evaluation to better determine its actual benefit. To fur-
ther evaluate the role of adjuvant chemotherapy, a
prospective randomized clinical trial for high-risk groups
is needed.
Footnote
a SAS system, SAS Institute, Cary, NC
Acknowledgments
The authors thank Drs Christine Bohn at the VCACat
Hospital of Philadelphia (Philadelphia, PA); Craig A.
Clifford and Suzanne Rau at Red Bank Veterinary Hos-
pital (Tinton Falls, NJ); Michael S. Kent and Genevieve
M. Hammond at the School of Veterinary Medicine,
University of California (Davis, CA); John McCauley at
the Cat Clinic at Cherry Hill (Cherry Hill, NJ); Andrea
Niggemeier at Old Marple Veterinary Hospital (Spring-
field, PA); Gerry A. Polton at Davies Veterinary
Specialists (Higham Gobion, Hertfordshire, UK); and
Laura Simon Treml at the University of Pennsylvania
(Philadelphia, PA) for their contribution to this study.
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