Chemotherapy Protocols for Dogs with Lymphoma: One Size Does Not Fit All!! :: Veterinary Cancer Specialists

Robyn Elmslie, DVM DACVIM (Oncology)

Veterinary Cancer Specialists at VRCC

Lymphoma is a lymph node cancer in dogs, similar to non-Hodgkin
lymphoma in people, and affects approximately 15% of dogs with
cancer.  It is rapidly progressive without treatment and very
difficult to cure. Chemotherapy continues to be the treatment
of choice for dogs with lymphoma.  The most commonly used
chemotherapy protocols consist of a combination of chemotherapy
drugs, most of which are given by injection. The goal is to combine
chemotherapy drugs with different mechanisms of action for killing
cancer cells, which in turn increases the probability of inducing a
complete remission and long-term survival.  At the same time,
combination chemotherapy protocols increase the time it takes for
the cancer cells to become resistant to treatment.  Many
variations of these multidrug protocols exist but the most widely
used is a combination of doxorubicin, vincristine, prednisone and
cyclophosphamide, known as CHOP. Treatment with CHOP has been
reported to result in median remission times of 174 to 204 days
 (Hosoya et al JVIM 2007; Simon et al JAVMA 2008) and to
result in median survival times of 275-322 days. While some CHOP
treated lymphoma patients have very short remission and survival
times, 26% of dogs treated with CHOP live more than 2 years (Simon
et al JAVMA 2008). 

Much research effort has been devoted to trying to understand
why some patients with lymphoma respond so well to treatment,
whereas others respond so poorly.  Several factors have been
identified that negatively impact outcomes in dogs with lymphoma
treated with chemotherapy.  One of the most important factors
is the type of lymphocyte from which the lymphoma arises (Marconato
et al. JAVMA 2011).  Lymphomas are broadly categorized into
B-cell and T-cell lymphoma. It is generally accepted and
widely reported in the literature that dogs with T cell lymphoma do
much more poorly than dogs with B cell lymphoma, when treated with
the CHOP protocol.  Beaver et al., first reported in 2009
(Veterinary Cancer Society Conference, Oct 2009), that one of the
key drugs in the CHOP protocol, doxorubicin, was poorly effective
for the treatment of T-cell lymphoma in dogs, and therefore may
explain why dogs with T cell lymphoma have been reported to have
short remission and survival times when treated with
CHOP.  In their study, Beaver et al. treated 29 dogs with
B-cell lymphoma and 12 dogs with T-cell lymphoma with doxorubicin
as the first chemotherapy drug, to assess response to
treatment.  Complete remission was achieved in 86.2% of dogs
with B-cell lymphoma after just one treatment with doxorubicin
whereas only 17% (2/12) of dogs with T-cell lymphoma achieved a
complete remission after one treatment of doxorubicin. In a
standard CHOP protocol, patients are treated with a different
chemotherapy drug each week for the first 4 weeks of the
protocol.  Doxorubicin is typically given on the third or 4
week of the protocol.  By this time, most patients with
lymphoma, regardless of whether they have T or B cell lymphoma, are
already in remission and therefore the actual benefit of
doxorubicin in the CHOP protocol cannot be directly
measured. 

Does this mean that dogs with T cell lymphoma should never be
treated with doxorubicin or CHOP? 

Rebhun et al (VCO 2011) recently reported a median remission of
104 days and a median survival time of 235 days in 24 dogs with T
cell lymphoma treated with CHOP.  In this study, Rebhun
reported that 14% of patients lived one year and 5 % of patients
lived 2 years. Brodsky et al (VCS 2009) reported more favorable
results for patients with T cell lymphoma in a study of 50 dogs
treated with an alternative protocol known as L-MOPP.  In this
study, 25% of dogs with T cell lymphoma were reported to survive
more than 2.5 years. 

There is not currently consensus in the Veterinary Oncology
community regarding the best chemotherapy protocol for the
treatment of patients with T cell lymphoma.  At Veterinary
Cancer Specialists at VRCC, we continue to treat each patient as an
individual.  There is not one approach that is best for every
patient.  Many factors must be considered in making treatment
recommendations.  As new research information becomes
available, we incorporate that knowledge into our recommendations
for our patients and their owners.  To learn more about Dr.
Elmslie, the Oncology Team and cancer treatments, please visit
www.vetcancerspecialists.com  and www.vrcc.com.  

Positive association between a glutathione-S-transferase polymorphism and lymphoma in dogs - Ginn - 2012 - Veterinary and Comparative Oncology

How to Cite

Ginn, J., Sacco, J., Wong, Y. Y., Motsinger-Reif, A., Chun, R. and Trepanier, L. A. (2012), Positive association between a glutathione-S-transferase polymorphism and lymphoma in dogs. Veterinary and Comparative Oncology. doi: 10.1111/vco.12000

Author Information

1. 
   ¹

   Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA

   
   


2. 
   ²

   Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA

   
   

^* Correspondence address
Dr Lauren A. Trepanier
Department of Medical Sciences, School of Veterinary Medicine
University of Wisconsin-Madison
2015 Linden Drive
Madison, WI 53706–1102, USA
e-mail: latrepanier@vetmed.wisc.edu

DIAGNOSTIC ACCURACY OF GRAY-SCALE ULTRASONOGRAPHY FOR THE DETECTION OF HEPATIC AND SPLENIC LYMPHOMA IN DOGS - CRABTREE - 2010 - Veterinary Radiology & Ultrasound

Gray-scale ultrasonography is often used to screen for involvement of the liver and spleen in canine lymphoma patients but the utility of sonography for staging lymphoma has not been evaluated quantitatively. We performed abdominal sonography in 28 dogs with a confirmed diagnosis of lymphoma. Needle aspirates were obtained for cytology from three separate sites in the liver and three sites in the spleen and the sonographic appearance was noted at each site. Our hypothesis was that in dogs newly diagnosed with lymphoma, abnormal appearance of the liver or spleen on ultrasound examination is an indication that lymphoma is present in that organ. Cytologic evaluation was used as the gold standard. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of hepatic and splenic abnormalities seen on ultrasound for diagnosis of lymphoma were 72.7%, 80.6%, 77.4%, 76.3%, and 76.8% for the liver, respectively, and 100%, 23.3%, 64.6%, 100%, and 68.1% for the spleen, respectively. Based on these results, we recommend that aspirates be performed for detection of lymphoma in the spleen of dogs only when the spleen appears abnormal ultrasonographically and that cytology of the liver be performed, regardless of ultrasonographic appearance, to determine the presence or absence of lymphoma.

Use of Prednisone in Canine Lymphoma: Friend or Foe? :: Veterinary Cancer Specialists

Robyn Elmslie DVM DACVIM (Oncology)

Veterinary Cancer Specialists at VRCC

Prednisone is one of the most widely prescribed drugs in
veterinary medicine, and also one of the most controversial.
 Prednisone at high doses is extremely immune suppressive,
making it a key drug in the treatment of a wide variety of
inflammatory and immune-mediated diseases.  Prednisone can
also be life saving for dogs with Addison’s disease. 

In oncology, prednisone therapy is often a key component of
standard treatment protocols for dogs with newly diagnosed
lymphoma.  The primary reason prednisone is so widely used in
cancer is that it can bind to lymphoma cell membrane receptors and
trigger rapid tumor cell death.  In addition, prednisone
therapy in dogs with lymphoma exerts a number of other
benefits.  For one, prednisone dramatically reduces
inflammation and fever caused by malignant lymphoma cells as a
consequence of prednisone induced upregulation of expression of
anti-inflammatory proteins and down-regulation of expression of
pro-inflammatory proteins.  Administration of prednisone also
lowers blood calcium concentrations in animals with cancer-induced
hypercalcemia.  This effect is mediated by decreased bone
resorption of calcium, by blocking intestinal calcium reabsorption,
and by increasing kidney calcium excretion.  These combined
effects lead to a rapid decrease in blood levels of calcium in dogs
with hypercalcemia secondary to lymphoma.  Given the
therapeutic benefits of prednisone, the drug’s low cost, oral
formulation and widespread availability, it is no wonder that pet
owners and veterinarians both may be tempted to consider prednisone
as the first line treatment for dogs newly diagnosed with
lymphoma.

While prednisone sounds like a panacea for dogs with lymphoma,
there are other factors to be aware of when using prednisone. 
While approximately 50% of patients newly diagnosed with lymphoma
will have dramatic lymph node size regression and improvement in
symptoms after initiating treatment with prednisone, these benefits
in many patients are short lived.  Survival times in dogs with
lymphoma that are treated only with prednisone typically range from
1 -3 months, as compared to 10 to 15 months with other common
multidrug protocols.  While prednisone may initially result in
a partial remission of the lymphoma by killing many of the
malignant cells, those cells that are inherently resistant to the
prednisone will rapidly grow and mutate to become more aggressive
than the original lymphoma.  This phenomenon is also known as
a recurrence or relapse of the lymphoma.  This more aggressive
relapsed lymphoma is often resistant to future treatment with other
chemotherapy drugs, resulting in short remission and survival times
for the patient.  Klein et al. (Vet Can Soc Newsletter 199115,
22-23) reported that treatment with prednisone for 2 weeks resulted
in increased resistance to future treatment with chemotherapy.

Treatment with prednisone can also negatively impact the ability
to make a definitive diagnosis of lymphoma.  If prednisone
treatment triggers dramatic lymph node size reduction, there may
not be adequate numbers of lymphoma cells to make a definitive
diagnosis using standard tests such as lymph node cytology, biopsy,
flow-cytometry or PCR.  The clinician and pet owner are then
faced with the dilemma of deciding whether to proceed with
chemotherapy without a definitive diagnosis, or to discontinue
prednisone and risk recurrence of a chemotherapy-resistant form of
lymphoma.  If a definitive diagnosis has been made, staging
completed and tissue for immunotyping has been collected, treatment
with prednisone for a few days is reasonable and not risky,
particularly if the patient is not feeling well or if treatment
with chemotherapy cannot be immediately initiated.

The most common side effects associated with prednisone
treatment noted in our patients with lymphoma consist of increased
urination and thirst, increased hunger and weight gain, and
panting.  While unpleasant, these side effects are typically a
reasonable trade off for the marked improvement in quality of life
noted once treatment is initiated.  When prednisone is used
for the treatment of lymphoma in combination with chemotherapy
drugs, the prednisone treatment is generally tapered off after a
few weeks and thus side effects resolve.

The most devastating side effect noted in our oncology patients
on long-term prednisone therapy is muscle wasting, which can result
in severe hind limb weakness, decreased stamina and perceived
decrease in quality of life despite the patient achieving complete
remission of the lymphoma.  Less common side effects include
painful calcinosis cutis, skin infections, marked elevations in
liver enzymes and poor hair coat.

At Veterinary Cancer Specialists, our guiding principle is that
quality of life should come first.  The appropriateness of
prednisone treatment for the individual patient must be considered
along with the optimal dose and treatment duration.  With this
in mind, prednisone treatment is customized for the cancer patient
and can be used safely, as part of a comprehensive treatment
plan.

For more information about our Oncology Team, our patients and
other Oncology topics, please visit www.vetcancerspecialists.com/resources, www.facebook.com/veterinarycancerspecialists.com
and www.vrcc.com/oncology.

Upstate Veterinary Specialists | Lymphoma

It is not known why certain dogs develop lymphoma, and others do not. In some dogs, there is an underlying genetic component, and in others, there are no predisposing factors (most common). For cats, studies have shown that cats living in smoking households are 2.5 times more likely to develop lymphoma than cats living in nonsmoking households. Lymphoma usually arises in the lymphoid tissues of the body (lymph nodes, spleen, and bone marrow), though lymphoma can affect any part of the body. The most common presentation of lymphoma for dogs is enlargement of all of the lymph nodes that you can feel. The enlarged lymph nodes are usually not painful. Cats usually do not present with enlarged lymph nodes that you can feel. Often cats will have lymphoma in their gastrointestinal tract and will present to the veterinarian for vomiting, diarrhea, weight loss, or a decreased appetite. Cats and dogs can also have lymphoma in their thoracic (chest) cavity, and they may have difficulty breathing.

Diagnostics

Blood samples (complete blood count and serum chemistry profile) and a urinalysis will be performed to determine your pet’s overall health status. Chest radiographs (x-rays), abdominal radiographs, and/or an abdominal ultrasound will be performed to look for involvement of certain organs with lymphoma. A fine needle aspirate may be performed of a lymph node to confirm the diagnosis of lymphoma. This is not painful for your pet. A bone marrow aspirate may also be performed looking for infiltration of lymphoma into the bone marrow. Your pet will be given an injection for pain before the procedure and will be under light anesthesia during the procedure. The procedure is usually performed from either the right or left front leg. Most dogs are not lame from the bone marrow aspirate, but your pet may be sleepy from the anesthesia, so it is important to keep them confined to a small area and avoid steps or walking the evening of the procedure. Occasionally a biopsy of a lymph node is needed to confirm the diagnosis and this is typically performed at the same time as the bone marrow aspirate.

Recommendations

Your pet’s oncologist will usually recommend that your pet be treated with systemic chemotherapy because lymphoma is always considered a systemic disease. Rarely would surgery and/or radiation therapy be utilized for lymphoma, but in certain cases, these modalities are recommended with concurrent chemotherapy. Occasionally, surgery is needed if the lymphoma is causing a blockage in the gastrointestinal tract. If surgery and/or radiation therapy are recommended, we will provide handouts to you and speak more about the specifics regarding these treatments.

Prognosis

Without any treatment, the average survival for dogs with lymphoma is 4 to 6 weeks. Approximately 50% of dogs with lymphoma will respond to prednisone (a steroid) alone, but the remission times are only 2 to 4 months with prednisone alone. Most dogs and cats with lymphoma respond very well to chemotherapy and go into a state of remission. Approximately 10% of dogs with lymphoma are cured, so a “cure” is rare. Remission is defined as the disappearance of the signs and symptoms of lymphoma in response to treatment. Our goal with chemotherapy is to obtain a remission, meaning that the lymphoma is under control and not detectable, but the disease is still present.

In general, the remission time in cats is not as long as in dogs, but we certainly have had cats that do very well for quite some time. Prognosis is more difficult to determine for cats since the staging system and prognostic factors are not as well defined as they are for dogs. One important prognostic factor for cats is how well they respond to initial chemotherapy (if they go into a state of remission). The average remission times for cats with lymphoma with treatment are generally 7 to 9 months, but this varies tremendously from cat to cat.

Prednisone will cause your pet to urinate more, drink more, pant more, and may increase the appetite. Please be sure that he/she has free choice water at all times and goes outside frequently to urinate. Your pet may NOT receive any aspirin or aspirin like products such as Carprofen (Rimadyl (R)), Deracoxib (Deramaxx (R)), Etodolac (Etogesic (R)), Piroxicam (Feldane (R)), Tepoxalin (Zubrin (R)), Meloxicam (Metacam (R)), while receiving prednisone, for the combination could cause a stomach ulcer. Most dogs will be weaned off the