WHAT’S NEW IN THE TREATMENT OF CANCER IN ANIMALS
Laurel Williams, DVM, DACVIM (Oncology)
North Carolina State University
INTRODUCTION
"Evaluation and treatment of dogs and cats with
cancer is increasingly common due to our
expanding knowledge of tumor biology and treatment m
odalities and clients’ willingness to pursue more
advanced care for their pets. New developments in di
agnosis and treatment are continuous. This lecture
will focus on a few of these new developments
DIAGNOSTICS
The first step in making a diagnosis of neoplasia
is aspiration cytology, although histopathology is
needed for both definitive diagnosis and information on tumor grade. In addition to these commonly used
tools, additional tests are available
that can provide further information.
In the case of round cell tumors,
one such valuable tool is PARR (PCR for Antigen Receptor Rearrangement). This test can be used in
both dogs and cats to determine whether lymphoid
neoplasia present, to determine the phenotype (B-
versus T-cell), and to monitor for the presence of mi
nimal residual disease in patients being treated for
lymphoma. This test utilizes genomic DNA and PCR
primers specific for B- and T-cell receptor gene
segments in canine and feline lymphocytes. The main
advantage of PARR is its ability to differentiate a
monoclonal (neoplastic) lymphoid proliferation from
a polyclonal (reactive) lymphoid proliferation,
although it is always prudent to interpret PARR data in
conjunction with other findings, including history,
clinical signs, cytology, flow cytometry and i
mmunocytochemistry. In dogs, PARR has a reported
sensitivity and specificity of approximately 90%. In cats
, its sensitivity and specificity are slighty better for
T-cell (89% and 80%, respectively) than B-cell neoplas
ia (60%, 70%, respectively). PARR can be run on
a variety of tissues, including lymph node aspirate
s, bone marrow aspirates, cellular effusions, blood,
cytology slides, formalin fixed tissues (25 micron sect
ions) and fresh frozen tissues (25 micron sections at
-80 degrees).
TREATMENT
Multi- and Novel Modality Treatment for Canine Lymphoma
Chemotherapy is considered standard therapy
for the treatment of canine lymphoma. However,
the use of chemotherapy in combination with other
treatment modalities is being investigated with the
hope of improving remission rates and duration.
Single-agent chemotherapy
Early reports focused on the use of singl
e agents including prednisone, L-asparaginase,
cyclophosphamide, and doxorubicin. Response rates range from approximately 20-80% with remission
durations of approximately 1-6 months.
Combination chemotherapy
Attempts to improve remission rates and
duration have been made through the use of
combination chemotherapy. Numerous protocols have
been reported with variations in scheduling, drug
dosages, and dose intensity, although most have
utilized induction chemotherapy followed by
maintenance chemotherapy. The drugs most commonl
y used in these protocols include prednisone, L-
asparaginase, vincristine, cyclophosphamide, and doxo
rubicin. Complete response rates range from
approximately 65-90% with remission dura
tions of approximately 6-11 months.
Pulse chemotherapy
Evidence from human oncology has suggested t
hat the use of discont
inuous chemotherapy,
rather than the traditional approach of using i
nduction chemotherapy followed by maintenance
chemotherapy, may provide comparable remission durati
on. Various reports in the veterinary literature
have attempted to determine whether this is also tr
ue in veterinary oncology. Moore et al reported on 82
dogs treated with a 15-week discontinuous, or pulse,
chemotherapy protocol consisting of prednisone, L-
asparaginase, vincristine, cyclophosphamide, and doxor
ubicin. This group of dogs was compared to dogs
previously treated with the same 15-week inducti
on followed by maintenance chemotherapy. This study
found no significant difference between the overa
ll protocol remission duration between these two
protocols. Similar findings were reported in a study by Garrett et al.
Radiation therapy
Given the lack of appreciable differences
among the various combination chemotherapy
protocols, new approaches to the treatment of c
anine lymphoma are aimed at investigating adjuvant
treatment modalities. Williams et al reported on 52 d
ogs treated with 11 weeks
of induction chemotherapy
consisting of prednisone, L-asparaginase, vincrist
ine, cyclophosphamide, and doxorubicin followed by
cranial and, three weeks later, caudal half-body r
adiation therapy. This protocol was well tolerated and
the reported median overall remission was 16.2 months
. Optimizations of combined modality therapy may
yield improvements in maintaining long-term remission.
Bone marrow transplantation
Given the apparent “ceiling” that has been reac
hed with chemotherapy, another new treatment
approach involves the use of bone marrow transplantati
on. Over the years, it
has been shown that dogs
can be given otherwise lethal doses of chemothera
py or radiation therapy and rescued via bone marrow
transplantation, and this treatment has the potential to
cure dogs of their disease. Based on this and
under the direction of Dr. Steve Suter, North Ca
rolina State University launched a bone marrow
transplantation treatment unit in the fall of 2008. D
ogs who have received combination chemotherapy and
are in complete remission are eligible for transplantati
on. The transplantation protocol consists of an initial
high-dose chemotherapy treatment to eradicate
any remaining tumor cells, followed by daily
administration of G-CSF to stimulate bone marrow st
em cells. Peripheral blood mononuclear cells are
then harvested via leukaphoresis, the dogs are treat
ed with near lethal doses of radiation therapy and
their harvested cells returned to them for engraftment and bone marrow recovery. Successful recovery
and extended survival has been seen in many case
s with new transplant patients being treated
approximately every 2-3 weeks. Ongo
ing patient evaluation will be needed to determine the optimal role
of this novel canine therapy.
Multi-modality Treatment for Feline Lymphoma
Chemotherapy is considered standard therapy fo
r the treatment of feline lymphoma, with the
possible exception of nasal ly
mphoma, which may be treated with radiation therapy.
Single-agent chemotherapy
Reports on single agent chemotherapy incl
uding prednisone, doxorubicin, and mitoxantrone
describe response rates ranging from 9-40% with re
mission durations ranging from 3-12 months. While
prednisone may be used as a single-agent, its use prio
r to the initiation of other chemotherapy use should
be avoided since this may decrease response rate and duration to other agents.
Combination chemotherapy
Improved remission rates and duration can be
achieved with combination chemotherapy.
Numerous protocols have been reported with variations
in scheduling, drug dosages, and dose intensity,
although most utilize induction followed by maintenance chemotherapy.
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